Biology subjects

Rahman, N.

Publications and source records attributed to Rahman, N..

At least 19 recordsLinked to original sources

bioRxiv2026

Optimizing a Culture-Enriched Hybrid Metagenomics Pipeline to Assess the AMR Footprint of Livestock Manure in Anaerobic Digestate

The role of environmental samples from livestock production systems, including manure and anaerobic digestate, as reservoirs of antimicrobial resistance genes (ARGs) is likely underestimated because conventional metagenomic approaches can overlook low-abundance ARGs and often lack the resolution needed to reliably associate these genes with their microbial hosts and linked mobile genetic elements (MGEs). Here, we evaluated whether culture-enriched metagenomics (CEMG), with and without antibiotic selection, enhances ARG detection in anaerobic digestate and improves the resolution of ARG-MGE-host associations using hybrid short- and long-read metagenomic assembly. Culture enrichment substantially increased ARG recovery, mean ARG abundance rose from 15.4 counts per million (CPM) in culture-independent direct metagenomes from fresh digestate (FD) to 124 CPM in CEMG without antibiotics and 160.0 CPM in antibiotic-selective CEMG, corresponding to an approximately 10.4-fold increase over FD. In FD, only 9 unique ARGs were detected, whereas enrichment recovered 112, including ARGs of clinical importance such as glycopeptide resistance, {beta}-lactamase genes of the CTX-M, OXA, and TEM families, and the cfr 23S rRNA methyltransferase conferring cross- resistance to multiple antibiotic classes. Oxygen availability was the strongest factor structuring enriched community compositions and ARG profiles, with aerobic and anaerobic communities forming distinct clusters. Antibiotic selection induced targeted, class-specific shifts in ARG profiles, with ARGs associated with tetracycline resistance consistently enriched across treatments. Hybrid metagenomic assembly resolved the genomic context of 784 ARGs, of which 59.3% were co-localized with at least one class of mobile genetic element (MGE), predominantly plasmids, insertion sequences, and integrative and conjugative/mobilizable elements (ICEs/IMEs). Biocide and metal resistance genes frequently co-occurred with ARGs on the same contigs, highlighting the potential for co-selection. Together, these findings demonstrate that antibiotic-selective culture enrichment enhances resistome surveillance by improving detection of low-abundance ARGs, while hybrid assembly provides critical genomic context for assessing their mobility and host associations. IMPORTANCELivestock manure and its byproducts, such as anaerobic digestate, are recognized as important environmental reservoirs of antimicrobial resistance genes and resistant bacteria, yet current metagenomic approaches may underestimate this risk by failing to detect low abundance but clinically relevant ARGs. Here, we show that integrating culture enrichment with hybrid metagenomics improves ARG recovery and reveals ARG co-localization with mobile genetic elements and putative bacterial hosts. This approach captures a cultivable and condition- responsive fraction of the resistome that is not readily accessible through direct metagenomic sequencing alone, providing a more informative framework for environmental AMR surveillance.

microbiology↗

bioRxiv2026

Spatial Agent-Based Modeling and Interpretable Machine Learning Predict Combination Therapy Response in HER2-Heterogeneous Breast Cancer

HER2 heterogeneity and reversible phenotypic plasticity play a central role in breast cancer progression and therapeutic resistance, yet how their interaction shapes treatment response remains poorly understood. HER2-positive and HER2-negative tumor cell states can dynamically interconvert, enabling compensatory population shifts that undermine monotherapies targeting a single phenotype. Because stochastic lineage effects and local cell interactions are averaged out in mean-field population-level ODE models, we develop a spatially resolved agent-based model (ABM) of heterogeneous tumor growth. We consider paclitaxel, which is modeled to preferentially suppress HER2-positive proliferation, and Notch inhibition, which targets HER2-negative populations and alters phenotypic composition. Starting from single-cell lineages, we assess the ABM against theoretical predictions from a population-level switching model and against single-cell-derived experimental measurements, showing consistency with early lineage dynamics and long-term phenotypic equilibria. Simulation results show that monotherapies induce compensatory phenotypic shifts and spatial reorganization that permit tumor persistence. In contrast, combination therapy simultaneously targeting HER2-positive and HER2-negative populations disrupts phenotypic replenishment, fragments spatial structure, and can achieve sustained tumor control across a range of simulated tumor regimes and treatment strengths. Importantly, in matched tumors with identical geometry, total burden, and phenotype counts, peripheral enrichment of HER2-negative cells increased post-treatment escape under paclitaxel, whereas this spatial effect was nearly eliminated by combination therapy. To quantify robustness across heterogeneous tumor parameter regimes, we pair the ABM with an interpretable Random Forest surrogate. Using only pre-treatment and early-trajectory features, the surrogate discriminates sustained control from persistence across held-out simulated parameter regimes and identifies growth-rate asymmetries as dominant drivers of resistance. Together, this integrated mechanistic and data-driven framework clarifies how HER2-mediated plasticity, spatial organization, and competitive growth dynamics shape therapy resistance and provides a scalable approach for analyzing simulated treatment responses across heterogeneous tumor regimes.

cancer biology↗

bioRxiv2026

High-throughput SWCNT NIR-II screening enables cell and in vivo applications

Diagnostic sensor development and clinical translation lag, in part, due to a lack of rapid, high-throughput screening methodology. Optimization of high-throughput sensor development and deployment will likely help in expediting tools toward the clinic. To address this issue, we optimized high-throughput screening parameters using a near-infrared (NIR-II) plate reader attached to an external probe for in vivo testing. We assessed spectroscopy parameters to improve speed and precision in screening a single-walled carbon nanotube (SWCNT)-based optical sensor. To do so, we assessed the appropriate well plate specifications, including laser power, excitation wavelength, exposure time, and focal height parameters for SWCNT-based optical sensor development. We also used the plate reader to screen fluorescent SWCNT which were endocytosed by a macrophage cell line. We then performed NIR probe spectroscopy to assess SWCNT embedded within a methylcellulose hydrogel. Finally, we used the NIR probe to measure SWCNT center wavelength and intensity from live immunocompetent mice. We anticipate that this framework may be broadly applicable to the development of near infrared nanosensors with the potential for more rapid clinical diagnostic translation.

bioengineering↗

bioRxiv2025

Phenotypic Plasticity and Competition Shape Therapy Sequencing in HER2+/HER2 Breast Cancer: A Mathematical Framework

Tumour heterogeneity and phenotypic plasticity are major drivers of treatment failure in cancer, enabling rapid adaptation under therapeutic pressure. In HER2-positive (HER2+) breast cancer, tumours often contain both HER2+ and HER2-negative (HER2-) cells whose interactions complicate schedule design. We develop a compact ordinary differential equation framework for intratumoral HER2+/- dynamics that integrates phenotypic plasticity with density-dependent growth and inter-phenotype competition. Phenotype-specific therapies are incorporated through simple pharmacodynamic surrogates: Paclitaxel chemotherapy acting primarily on HER2+ cells and Notch-pathway inhibition targeting HER2- cells. We use the model to compare staggered and simultaneous treatment schedules. The results show that treatment order and relative intensity critically shape long-term tumour composition. Targeted-first schedules can exhibit competitive release, whereby subsequent aggressive chemotherapy unintentionally favours HER2- expansion. In contrast, simultaneous initiation suppresses both phenotypes more effectively and avoids strong rebound. These findings highlight the importance of ecological structure in therapy design and support simultaneous combination therapy followed by targeted maintenance.

cancer biology↗

bioRxiv2025

Genome writing to dissect consequences of SVA retrotransposon disease X-Linked Dystonia Parkinsonism

Human retrotransposon insertions are often associated with diseases. In the case of the neurodegenerative X-Linked Dystonia-Parkinsonism disease, a human-specific SINE-VNTR-Alu subfamily F retrotransposon was inserted in intron 32 of the TAF1 gene. Here, we genomically rewrote a portion of the mouse Taf1 allele with the corresponding 78-kb XDP patient derived TAF1 allele. In mESCs, the presence of the intronic SVAs--rather than the hybrid gene structure--reduces hyTAF1 levels. This leads to transcriptional downregulation of genes with TATA box enriched in their promoters and triggering apoptosis. Chromatin and transcriptome profiling revealed that intronic SVAs are actively transcribed, forming barriers that likely impede transcription elongation. In mice, neuronal lineage TAF1 humanization resulted lethality of male progeny within two months. XDP male mice had severe atrophy centered on the striatum--the same affected brain region in XDP patients. Lastly, CRISPRa-mediated activation of hyTAF1 restored mESC viability, suggesting boosting TAF1 transcription as a therapeutic approach.

genetics↗

bioRxiv2025

Ontogeny Dictates Oncogenic Potential, Lineage Hierarchy, and Therapy Response in Pediatric Leukemia

Accumulating evidence links pediatric cancers to prenatal transformation events, yet the influence of the developmental stage on oncogenesis remains elusive. We investigated how hematopoietic stem cell developmental stages affect leukemic transformation, disease progression, and therapy response using a novel, humanized model of NUP98::NSD1-driven pediatric acute myeloid leukemia, that is particularly aggressive with WT1 co-mutations. Fetal-derived hematopoietic stem cells readily transform into leukemia, and WT1 mutations further enhance stemness and alter lineage hierarchy. In contrast, stem cells from later developmental stages become progressively resistant to transformation. Single-cell analyses revealed that fetal-origin leukemia stem cells exhibit greater quiescence and reliance on oxidative phosphorylation than their postnatal counterparts. These differences drive distinct therapeutic responses, despite identical oncogenic mutations. In patients, onco-fetal transcriptional programs correlate with worse outcomes. By targeting key vulnerabilities of fetal-origin leukemia cells, we identified combination therapies that significantly reduce aggressiveness, highlighting the critical role of ontogeny in pediatric cancer treatment.

cancer biology↗

bioRxiv2024

Chronic High Intensity Interval Training (HIIT) exercise in adolescent rat's result in cocaine place aversion and ΔFosB induction

High-Intensity Interval Training (HIIT) is a form of exercise that has been greatly popularized over the past few years for its many health benefits. Similar to other forms of exercise, HIIT may be beneficial in the prevention of substance use behaviors; however, the extent to which HIIT can impact the reinforcing effects of drugs of abuse during adolescence has not been fully evaluated. Here, we assess the effects of HIIT during adolescence on subsequent cocaine conditioned place preference (CPP) in male Lewis rats. The HIIT exercise exposed rats ran on a treadmill for 30 minutes daily (ten three-minute cycles) for six weeks with progressive speed-increased up to 0.8 mph (21.5m/min), while the sedentary rats remained in their home cage. Following the six weeks of exercise, rats were tested for cocaine (25 mg/kg) CPP. Following completion of the behavior test {Delta}FosB levels were measured in the brain. Results showed that the HIIT rats showed significantly attenuated place preference (-19%) in their time spent in the cocaine-paired chamber compared to the sedentary environment rats. In addition, HIIT rats had significantly higher (65%) striatum {Delta}FosB levels compared to the sedentary rats. Our findings show that HIIT exercise during adolescence could be protective against cocaine abuse which may be mediated by an increase in {Delta}FosB. This finding has important clinical implications with respect to exercise mediated protection against substance misuse and abuse. Future studies will examine this effect in females as well as the potential underlying mechanisms.

neuroscience↗

bioRxiv2024

The Condensin II Complex Regulates the Expression of Essential Gene Expression Programs During Erythropoiesis

Erythropoiesis is characterized by dramatic changes in gene expression in the context of a cell that is rapidly proliferating while simultaneously condensing its nucleus in anticipation of enucleation. The mechanisms that maintain high level expression of erythroid genes and promote nuclear condensation remain poorly understood. Condensin II is a ring-like complex that promotes mitotic chromatin condensation and has roles in regulating interphase chromatin architecture and gene expression. We interrogated the role of Condensin II in erythropoiesis using an erythroid-specific deletion of the Condensin II subunit, Ncaph2. Ncaph2 loss resulted in severe embryonic anemia with lethality at embryonic day 13.5. Ncaph2 mutant erythroid cells had dysregulated maturation and disrupted cell cycle progression, but surprisingly Ncaph2 was dispensable for nuclear condensation. Genomic studies revealed that Ncaph2 occupied the promoter of key erythroid and cell cycle genes that were downregulated following Ncaph2 loss. Together, our results demonstrate an essential role for Ncaph2 in the gene expression programs that regulate cell cycle progression and erythroid differentiation, and identify a key role for the Condensin II complex in the regulation of a lineage-specific differentiation program. Summary StatementThe Condensin II complex regulates cell cycle progression and erythroid differentiation, but is dispensable for nuclear condensation during terminal erythroid maturation.

genomics↗

bioRxiv2024

Auditory working memory mediates the relationship between musicianship and auditory stream segregation

This study investigates the interactions between musicianship and two auditory cognitive mechanisms: auditory working memory (AWM) and stream segregation. The primary hypothesis is that AWM mediates the relationship between musical training and enhanced stream segregation capabilities. Two groups of listeners were tested, the first to establish the relationship between the two variables and the second to replicate the effect in an independent sample. Music history and behavioural data were collected from a total of 145 healthy young adults with normal binaural hearing. They performed a task that requires manipulation of tonal patterns in working memory, and the Music-in-Noise Task (MINT), which measures stream segregation abilities in a musical context. The MINT task expands measurements beyond traditional Speech-in-Noise (SIN) assessments by capturing auditory subskills (e.g., rhythm, visual, spatial, prediction) relevant to stream segregation. Our results showed that musical training is associated with enhanced AWM and MINT task performance, and that this effect is replicable across independent samples. Moreover, we found in both samples that the enhancement of stream segregation was largely mediated by AWM capacity. The results suggest that musical training and/or aptitude enhances music-in-noise perception by way of improved AWM capacity.

neuroscience↗

bioRxiv2024

Stretch-induced recruitment of myosin into transversal actin rings stabilizes axonal large cargo transport

We study the axonal transport of large cargo vesicles and its feedback with contractile transversal actomyosin rings in axons through modelling and simulation. To this end, we simulate a mathematical model that integrates forces generated by the molecular motors and forces exerted by transversal actin rings. Our results predict that cargo vesicles exhibit bidirectional movement along with pauses in agreement with observations. It has been observed that during predominantly retrograde axonal cargo transport, blebbistatin treatment prolongs the periods spent by the cargo in anterograde transport. Our simulations show that this can be explained by mechanotransductive stretch-induced recruitment of myosin motors into transversal actin rings. These findings offer valuable insights into the complex dynamics of axonal cargo transport and propose potential avenues for further experimental research.

biophysics↗

bioRxiv2024

Dlk1 is a novel adrenocortical stem/progenitor cell marker that predicts malignancy in adrenocortical carcinoma

Disruption of processes involved in tissue development and homeostatic self-renewal is increasingly implicated in cancer initiation, progression, and recurrence. The adrenal cortex is a dynamic tissue that undergoes life-long turnover. Here, using genetic fate mapping and murine adrenocortical carcinoma (ACC) models, we have identified a population of adrenocortical stem cells that express delta-like non-canonical Notch ligand 1 (DLK1). These cells are active during development, near dormant postnatally but are re-expressed in ACC. In a study of over 200 human ACC samples, we have shown DLK1 expression is ubiquitous and is an independent prognostic marker of recurrence-free survival. Paradoxically, despite its progenitor role, spatial transcriptomic analysis has identified DLK1 expressing cell populations to have increased steroidogenic potential in human ACC, a finding also observed in four human and one murine ACC cell lines. Finally, the cleavable DLK1 ectodomain is measurable in patients serum and can discriminate between ACC and other adrenal pathologies with high sensitivity and specificity to aid in diagnosis and follow-up of ACC patients. These data demonstrate a prognostic role for DLK1 in ACC, detail its hierarchical expression in homeostasis and oncogenic transformation and propose a role for its use as a biomarker in this malignancy. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/609117v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@12aba74org.highwire.dtl.DTLVardef@374daaorg.highwire.dtl.DTLVardef@cbdc37org.highwire.dtl.DTLVardef@1e6aeac_HPS_FORMAT_FIGEXP M_FIG C_FIG Statement of significanceThis study presents DLK1 as a novel biomarker in ACC with opportunities for use in the diagnosis, prognosis and longitudinal follow up of patients. DLK1, a marker of adrenocortical stem cells, is re-expressed in ACC, is measurable in patients serum and is associated with increased malignancy.

cancer biology↗

bioRxiv2024

Nanopore-based analysis unravels the genetic landscape and phylogenetic placement of human-infecting Trichuris species in Cote d'Ivoire, Tanzania, Uganda, and Laos

Soil-transmitted helminthiases, particularly trichuriasis, affect over 500 million people, mostly in low- and middle-income countries. Traditional diagnostics fail to distinguish between Trichuris species, obscuring transmission patterns and treatment outcomes. Using nanopore-based full-length ITS2 rDNA sequencing, we analyzed 687 samples from Cote dIvoire, Laos, Tanzania, and Uganda, confirming the phylogenetic placement of Trichuris trichiura and the recently described Trichuris incognita. We identified two genetically distinct Trichuris species infecting humans, with divergent geographic patterns and presence in non-human primates, suggesting complex host-parasite dynamics. Within-country genetic variation indicated local adaptation and cryptic population structure. Importantly, we demonstrated that ITS2 fragment length is a robust, cost-effective diagnostic marker for differentiating T. incognita and T. trichiura, offering a practical alternative to sequencing for resource-limited settings. These findings expose the hidden complexity of Trichuris infections and highlight the urgent need to update diagnostic and control strategies to account for overlooked species diversity in endemic regions.

genomics↗

bioRxiv2024

Rapid differentiation of estrogen receptor status in patient biopsy breast cancer aspirates with an optical nanosensor

Breast cancer is a substantial source of morbidity and mortality worldwide. It is particularly more difficult to treat at later stages, and treatment regimens depend heavily on both staging and the molecular subtype of the tumor. However, both detection and molecular analyses rely on standard imaging and histological method, which are costly, time-consuming, and lack necessary sensitivity/specificity. The estrogen receptor (ER) is, along with the progesterone receptor (PR) and human epidermal growth factor (HER-2), among the primary molecular markers which inform treatment. Patients who are negative for all three markers (triple negative breast cancer, TNBC), have fewer treatment options and a poorer prognosis. Therapeutics for ER+ patients are effective at preventing disease progression, though it is necessary to improve the speed of subtyping and distribution of rapid detection methods. In this work, we designed a near-infrared optical nanosensor using single-walled carbon nanotubes (SWCNT) as the transducer and an anti-ER antibody as the recognition element. The nanosensor was evaluated for its response to recombinant ER in buffer and serum prior to evaluation with ER- and ER+ immortal cell lines. We then used a minimal volume of just 10 {micro}L from 26 breast cancer biopsy samples which were aspirated to mimic fine needle aspirates. 20 samples were ER+, while 6 were ER-, representing 13 unique patients. We evaluated the potential of the nanosensor by investigating several SWCNT chiralities through direct incubation or fractionation deployment methods. We found that the nanosensor can differentiate ER-from ER+ patient biopsies through a shift in its center wavelength upon sample addition. This was true regardless of which of the three SWCNT chiralities we observed. Receiver operating characteristic area under the curve analyses determined that the strongest classifier with an AUC of 0.94 was the (7,5) chirality after direct incubation and measurement, and without further processing. We anticipate that further testing and development of this nanosensor may push its utility toward field-deployable, rapid ER subtyping with potential for additional molecular marker profiling.

bioengineering↗

bioRxiv2024

The inflammatory micro-environment induced by targeted CNS radiotherapy is underpinned by disruption of DNA methylation

Although targeted radiotherapy (RT) is integral to the increasing survival of cancer patients, it has significant side-effects, the cellular and molecular mechanisms of which are not fully understood. During RT epigenetic changes occur in neoplastic tissue, but few studies have assessed these in non-neoplastic tissue and results are highly variable. Using bulk DNA methylation and RNA sequencing as well as spatial transcriptomics (ST) in a unique cohort of patient tissue samples, we show distinct differences in DNA methylation patterns in irradiated brain tissue, whilst ST characterisation identifies specific micro-environmental niches present after irradiation and highlights neuropeptides that could be propagating neuroinflammation. We also show that in a cerebral organoid (CO) model of early changes in neurons after irradiation there are similar DNA methylation alterations and disruption of the DNA methylation machinery, suggesting that early but persistent epigenetic dysregulation plays a role in neurotoxicity. We provide a link between radiotherapy induced neuroinflammation and disruption of DNA methylation for the first time and suggest possible driving mechanisms for this chronic neuroinflammation.

neuroscience↗

bioRxiv2023

Human vaginal microbiota colonization is regulated by female sex 1 hormones in a mouse model

Clinically, a Lactobacillus rich vaginal microbiota (VMB) is considered optimal for reproductive outcomes, while a VMB populated by anaerobes is associated with dysbiosis and the clinical condition bacterial vaginosis (BV), which is linked to increased susceptibility to sexually transmitted infections and adverse reproductive outcomes. Mouse models that mimic eubiotic and dysbiotic VMB are currently lacking but could play a critical role in improving protective interventions. In this study, probiotic, eubiotic, and dysbiotic models were first developed in normal mice, using probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14, eubiotic Lactobacillus crispatus, or dysbiotic Gardnerella vaginalis strains. Following a single administration, L. rhamnosus and L. reuteri persisted in the mouse vaginal tract for up to eight days, L. crispatus persisted for up to three days, and G. vaginalis persisted for up to two days, as measured by quantitative plating assays and qPCR. Colonization of G. vaginalis was facilitated by the presence of mucin. Endogenous sex hormones were manipulated by either ovariectomizing (OVX) mice or administering 17{beta}-estradiol and progesterone pellets in OVX mice. The lack of endogenous hormones in OVX mice dramatically decreased VMB bacterial load compared to normal mice. None of the exogenous bacteria including Lactobacilli could colonize OVX mice for more than 24 hours. Treatment with 17{beta}-estradiol but not progesterone restored the endogenous microbiota and colonization with Lactobacilli and G. vaginalis. Interestingly, 17{beta}-estradiol treated mice had significantly increased levels of glycogen, compared to OVX and progesterone-treated mice. These results suggest there is a dynamic interaction between sex hormones and the VMB, which can affect bacterial diversity and the ability for a VMB to colonize.

microbiology↗

bioRxiv2023

Optical nanosensor passivation enables highly sensitive detection of the inflammatory cytokine IL-6

Interleukin-6 (IL-6) is known to a play critical role in the progression of inflammatory diseases such as cardiovascular disease, cancer, sepsis, viral infection, neurological disease, and autoimmune diseases. Emerging diagnostic and prognostic tools, such as optical nanosensors, experience challenges in successful clinical application in part due to protein corona formation dampening their selectivity and sensitivity. To address this problem, we explored the rational screening of several classes of biomolecules to be employed as agents in non-covalent surface passivation as a strategy to screen interference from non-specific proteins. Findings from this screening were applied to the detection of IL-6 by a fluorescent antibody-conjugated single-walled carbon nanotube (SWCNT)-based nanosensor. The IL-6 nanosensor exhibited highly sensitive and specific detection after passivation with a polymer, poly-L-lysine, as demonstrated by IL-6 detection in human serum within a clinically relevant range of 25 pg/mL to 25,000 pg/mL, exhibiting a limit of detection over three orders of magnitude lower than prior antibody-conjugated SWCNT sensors. This work holds the potential for rapid and highly sensitive detection of IL-6 in clinical settings with future application to other cytokines or disease-specific biomarkers.

bioengineering↗

bioRxiv2023

Mobilisation and analyses of publicly available SARS-CoV-2 data for pandemic responses

The COVID-19 pandemic has seen large-scale pathogen genomic sequencing efforts, becoming part of the toolbox for surveillance and epidemic research. This resulted in an unprecedented level of data sharing to open repositories, which has actively supported the identification of SARS-CoV-2 structure, molecular interactions, mutations and variants, and facilitated vaccine development and drug reuse studies and design. The European COVID-19 Data Platform was launched to support this data sharing, and has resulted in the deposition of several million SARS-CoV-2 raw reads. In this paper we describe (1) open data sharing, (2) tools for submission, analysis, visualisation and data claiming (e.g. ORCiD), (3) the systematic analysis of these datasets, at scale via the SARS-CoV-2 Data Hubs as well as (4) lessons learned. As a component of the Platform, the SARS-CoV-2 Data Hubs enabled the extension and set up of infrastructure that we intend to use more widely in the future for pathogen surveillance and pandemic preparedness.

bioinformatics↗

bioRxiv2023

A mathematical model for axonal transport of large cargo vesicles

In this study, we consider axonal transport of large cargo vesicles characterised by transient expansion of the axon shaft. Our goal is to formulate a mathematical model which captures the dynamic mechanical interaction of such cargo vesicles with the membrane associated periodic cytoskeletal structure (MPS). It consists of regularly spaced actin rings that are transversal to the longitudinal direction of the axon and involved in the radial contraction of the axon. A system of force balance equations is formulated by which we describe the transversal rings as visco-elastic Kelvin-Voigt elements. In a homogenisation limit, we reformulate the model as a free boundary problem for the interaction of the submembranous MPS with the large vesicle. We derive a non-linear force-velocity relation as a quasi-steady state solution. Computationally we analyse the vesicle size dependence of the transport speed and use an asymptotic approximation to formulate it as a power law that can be tested experimentally.

biophysics↗