Biology subjects

Mohseni, M.

Publications and source records attributed to Mohseni, M..

9 recordsLinked to original sources

bioRxiv2026

CellCage™ Technology Enables High-throughput Isolation of Defined Cell Combinations to Resolve the Determinants of CAR-T mediated Cytotoxicity

Understanding the cellular determinants of CAR-T cell-mediated cytotoxicity at the single-cell level remains a critical challenge in developing effective cellular immunotherapies. Conventional bulk co-culture assays provide only population-level measurements of cytotoxic activity and cannot resolve the functional heterogeneity of individual effector-target interactions. Here, we demonstrate the Cellanome platform, which enables the formation of CellCage Enclosures (CCEs) through spatially controlled photopolymerization, as a tool for high-resolution, high-throughput characterization of CAR-T cell-mediated cytotoxicity. By isolating defined effector-target combinations within individual CCEs and coupling encapsulation with longitudinal time-lapse imaging and automated image analysis, we resolve cytotoxic activity across thousands of individually tracked CCEs. Using anti-CD19 CAR-T effectors and NALM6-GFP targets, we show that individual CD8+ CAR-T effectors exhibit substantial functional heterogeneity, with serial killing capacity, effector-target contact dynamics, and intrinsic motility each independently correlating with cytotoxic potency. Cytotoxic efficacy scaled positively with effector number, and CD4+ T helper cells augmented CD8+-mediated killing in a dose-dependent manner, providing direct evidence for cooperative T cell behavior during tumor cell clearance. Extending the platform to a solid tumor model using AIC100 anti-ICAM-1 CAR-T cells and HeLa-GFP targets, we show that individual AIC100 effectors are insufficient to mediate effective killing, while multi-effector CCEs exhibit robust cytotoxicity scaling with effector abundance and CD4+:CD8+ composition. These data establish the Cellanome platform as a broadly applicable system for dissecting the determinants of CAR-T cell cytotoxicity at single-cell resolution, with direct translational relevance to the optimization of cellular immunotherapy.

immunology↗

bioRxiv2026

Scalable longitudinal imaging and transcriptomics of cells in dynamic enclosures

Dynamic transitions between cell states underlie both normal physiology and disease. However, most single-cell technologies capture only static snapshots. To address this gap, we developed a platform that integrates light-guided hydrogel polymerization with computer vision to generate on-demand compartments around live cells, enabling longitudinal imaging of cellular behavior paired with whole-transcriptome profiling of the same cells at scale. These data link dynamic phenotypes with molecular programs, enabling deeper characterization of cellular states. This approach revealed an adaptive, drug-resistant state in lung cancer cells characterized by potassium channel upregulation and p53-dependent quiescence. In models of adipogenesis and microglial phagocytosis, joint analysis of imaging and transcriptomic data identified key drivers of cellular function that were missed by transcriptomic clustering alone. These results establish the value of paired functional and transcriptomic analysis to resolve molecular drivers of complex cellular behaviors.

systems biology↗

bioRxiv2026

MMH: A multimodal dataset of whole-body kinematics, bilateral ground reaction forces, and lower-limb surface electromyography signals during load lifting and lowering

This study presents the MMH dataset, a laboratory-collected in vivo dataset comprising whole-body kinematics, three-dimensional ground reaction forces and two-dimensional centres of pressure under both feet, as well as surface electromyography (sEMG) signals of twelve lower-limb muscles (six muscles per leg) during load lifting and lowering tasks. Ten healthy, normal-weight, young male adults each performed 72 trials combining one- and two-handed load (2 kg) lifting and lowering. These trials include multiple initial and final load locations while using three different lifting techniques (stoop, semi-squat, and full-squat). The kinematic and force-plate measurements provide rich input for ergonomic risk assessment tools and optimisation-based musculoskeletal models aimed at quantifying and managing musculoskeletal risk of injury. Also, the sEMG recordings enable the development of EMG-assisted musculoskeletal models and support validation of predictions from optimisation-based models. These makes the multimodal MMH dataset a valuable resource for biomechanics, ergonomics, and human movement research.

bioengineering↗

bioRxiv2024

Measuring single-cell density with high throughput enables dynamic profiling of immune cell and drug response from patient samples

Cell density, the ratio of cell mass to volume, is an indicator of molecular crowding and therefore a fundamental determinant of cell state and function. However, existing density measurements lack the precision or throughput to quantify subtle differences in cell states, particularly in primary samples. Here we present an approach for measuring the density of 30,000 single cells per hour with a precision of 0.03% (0.0003 g/mL) by integrating fluorescence exclusion microscopy with a suspended microchannel resonator. Applying this approach to human lymphocytes, we discovered that cell density and its variation decrease as cells transition from quiescence to a proliferative state, suggesting that the level of molecular crowding decreases and becomes more regulated upon entry into the cell cycle. Using a pancreatic cancer patient-derived xenograft model, we found that the ex vivo density response of primary tumor cells to drug treatment can predict in vivo tumor growth response. Our method reveals unexpected behavior in molecular crowding during cell state transitions and suggests density as a new biomarker for functional precision medicine.

bioengineering↗

bioRxiv2021

Core bone diameter in an organic implant-less technique affecting the biomechanical properties of the anterior cruciate ligament fixation; an in-vitro study

BackgroundBone and site hold tendon inside (BASHTI) is an implant-less technique that can solve some of the problems associated with other anterior cruciate ligament (ACL) reconstructive methods. This study aims to investigate the effect of core bone diameter variation on the biomechanical properties of a reconstructed ACL using BASHTI technique. MethodsA number of 15 laboratory samples of reconstructed ACL were built using bovine digital tendons and Sawbones blocks. Samples were divided into three groups with different core bone diameters of 8 mm, 8.5 mm, and 9 mm. The double-stranded tendon size and bone tunnel diameter were 8 mm and 10 mm, respectively. A loading scenario consisting of two cyclic loadings followed by a single cycle pull-out loading was applied to the samples simulating the after-surgery loading conditions to observe the fixation strength. ResultsResults showed that the core bone diameter had a significant effect on the failure mode of the samples (P = 0.006) and their fixation strength (P < 0.001). Also, it was observed that the engaging length and the average cyclic stiffness (ACS) of them were influenced by the core bone diameter significantly (engaging length: P = 0.001, ACS: P = 0.007), but its effect on the average pull-out stiffness was not significant (P = 0.053). ConclusionsIt was concluded that core bone diameter variation has a significant impact on the mechanical properties of ACL reconstruction when BASHTI technique is used, and it should be noted for surgeons who use BASHTI technique. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/452098v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@33ca50org.highwire.dtl.DTLVardef@276f38org.highwire.dtl.DTLVardef@f6e66forg.highwire.dtl.DTLVardef@192b117_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIA new implant-less technique was used to reconstruct anterior cruciate ligament. C_LIO_LIArtificial bone and fresh animal soft tissue used to simulate the fixation process. C_LIO_LILoading condition were carefully chosen to simulate the post-operation. C_LIO_LIComponents geometry had direct effect on biomechanical properties of the fixation. C_LIO_LIOptimum geometry was found trough an experimental examination. C_LI

bioengineering↗

bioRxiv2020

Biomechanical Modeling of a Bone Tunnel Enlargement Post ACL Reconstruction

BackgroundBone tunnel enlargement is considered as a potential problem following ACL reconstruction and can cause a fixation failure and complicate its revision surgery. This study evaluates post tibial tunnel expansion in ACL reconstruction using an interference screw. MethodsA series of in-vitro experimental tests on animal bone and tissues were used to simulate post ACL reconstruction. The study believes an unbalanced lateral force can cause a local enlargement on the contact zone inside the tunnel. Grayscale X-ray images were used to assess the screw alignment inside the tunnel. ResultsThey showed a slight misalignment between the screw and the tunnel axis as the tendon strands moved along the side of the tunnel, and the screw had partial contact with the tendon and bone along the tunnel. According to the results, increased stress in the tunnel wall causes tunnel enlargement. Although the tunnel created away from the tibial central axis produced a higher strength, it results in higher stress on the wall of the tunnel which can increase the risk of tunnel expansion. ConclusionsThe current study believes the use of an unguided interference screw insertion potentially increases risks of the misaligned fixation and cause a tunnel enlargement. This risk may be controlled by restricting the post-operative rehabilitation.

bioengineering↗

bioRxiv2020

Comparing DNA Extraction and 16s Amplification Methods for Plant-Associated Bacterial Communities

Plant-associated microbes play important roles in global ecology and agriculture. The most common method to profile these microbial communities is amplicon sequencing of the bacterial 16s rRNA gene. Both the DNA extraction and PCR amplification steps of this process are subject to bias, especially since the latter requires some way to exclude DNA from plant organelles, which would otherwise dominate the sample. We compared several common DNA extraction kits and 16s rRNA amplification protocols to determine the relative biases of each and to make recommendations for plant microbial researchers. For DNA extraction, we found that, as expected, kits optimized for soil were the best for soil, though each still included a distinct "fingerprint" of its own biases. Plant samples were less clear, with different species having different "best" options. For 16s amplification, we find that using peptide nucleic acid (PNA) clamps provides the least taxonomic distortion, while chloroplast-discriminating primers are easy and inexpensive but present significant bias in the results. We do not recommend blocking oligos, as they involved a more complex protocol and showed significant taxonomic bias in the results. Further methods development will hopefully result in protocols that are even more reliable and less biased.

microbiology↗

bioRxiv2019

Time resolved quantitative phosphoproteomics reveals distinct patterns of SHP2 dependence in EGFR signaling

SHP2 is a protein tyrosine phosphatase that normally potentiates intracellular signaling by growth factors, antigen receptors, and some cytokines; it is frequently mutated in childhood leukemias and other cancers. Here, we examine the role of SHP2 in the responses of breast cancer cells to EGF by monitoring phosphoproteome dynamics when SHP2 is allosterically inhibited by the small molecule SHP099. Data on phosphotyrosine abundance at more than 400 tyrosine residues reveals six distinct response signatures following SHP099 treatment and washout. These include putative substrate sites with increased phosphotyrosine abundance at early or late timepoints, and another class of sites that shows reduced phosphotyrosine abundance when SHP099 is present. Sites of decreased phospho-abundance are enriched on proteins with two nearby phosphotyrosine residues, which can be directly protected from dephosphorylation by the paired SH2 domains of SHP2 itself. These findings highlight how analysis of phosphoproteomic dynamics can provide insight into transmembrane signaling responses.

cell biology↗

bioRxiv2018

ATRAID, a genetic factor that regulates the clinical action of nitrogen-containing bisphosphonates on bone.

Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, are the most widely prescribed medications for diseases involving bone, with nearly 200 million prescriptions written annually. Recently, widespread use of N-BPs has been challenged due to the risk of rare but traumatic side effects such as atypical femoral fracture (AFFs) and osteonecrosis of the jaw (ONJ). N-BPs bind to and inhibit farnesyl diphosphate synthase (FDPS), resulting in defects in protein prenylation. Yet it remains poorly understood what other cellular factors might allow N-BPs to exert their pharmacological effects. Here, we performed genome-wide studies in cells and patients to identify the poorly characterized gene, ATRAID. Loss of ATRAID function results in selective resistance to N-BP-mediated loss of cell viability and the prevention of alendronate-mediated inhibition of prenylation. ATRAID is required for alendronate inhibition of osteoclast function, and ATRAID-deficient mice have impaired therapeutic responses to alendronate in both postmenopausal and senile (old age) osteoporosis models. Lastly, we performed exome sequencing on patients taking N-BPs that suffered ONJ or an AFF. ATRAID is one of three genes that contain rare non-synonymous coding variants in patients with ONJ or AFF that is also differentially expressed in poor outcome groups of patients treated with N-BPs. We functionally validated this patient variation in ATRAID as conferring cellular hypersensitivity to N-BPs. Our work adds key insight into the mechanistic action of N-BPs and the processes that might underlie differential responsiveness to N-BPs in people. One Sentence SummaryATRAID is essential for responses to the commonly prescribed osteoporosis drugs nitrogen-containing bisphosphonates. OverlineBONE

genomics↗