Biology subjects

Sarikhani, E.

Publications and source records attributed to Sarikhani, E..

6 recordsLinked to original sources

bioRxiv2026

A predictive mechanochemical modeling framework for the deformation and remodeling of the nuclear lamina

1Nuclear envelope stretch and rupture are common to cell spreading and migration in a variety of microenvironments, leading to marked changes in nucleocytoplasmic transport. Predicting cell response to different mechanochemical cues that are transmitted to the nucleus remains an open problem in the field of mechanomedicine. We developed a predictive modeling framework to examine how nuclear deformation on substrates with different nanotopographies influences nucleocytoplasmic transport and rearrangement of the nuclear lamina. Using the finite element method, we simulated nuclear compression by the perinuclear actin cap on substrates with arrays of nanopillars, modeling the nuclear envelope as a nonlinear elastic structure and coupling deformations to a biochemical model of lamin remodeling and nucleocytoplasmic transport. These simulations predicted regions of high nuclear envelope stretch adjacent to cell-nanopillar contacts, leading to maximized nuclear envelope tension on small nanopillars spaced by 4-5 microns. We then considered the effects on nuclear transport of YAP and TAZ and found that increased nuclear compression led to YAP/TAZ nuclear localization in agreement with previous experiments. Furthermore, the simulated force load per lamin was maximized on nanopillar substrates with high nuclear stretch. The magnitude of this load was modulated by the rate of actin cap assembly and the overall expression level of lamin A/C - decreasing lamin content in the nuclear envelope led to a higher likelihood of rupture. We validated this prediction in subsequent experiments with lamin-depleted U2OS cells, establishing the central importance of lamin transport and microenvironment nanotopography to nuclear mechanotransduction. 2 SignificanceCell nuclei commonly experience large strains, but existing computational models do not explain the coupling between such deformations and molecular transport. Here, we present a modeling framework that includes the mechanics of nuclear deformations and the reaction-transport of molecules within the cytoplasm, nuclear envelope, and nuclear interior. As a well-controlled setup for comparing experiments and simulations, we consider nuclear indentations exhibited by cells on nanopillar substrates. Our simulations recapitulate measurements of nuclear YAP/TAZ localization from the literature and predict that low-lamin cells experience higher force loads at the nuclear envelope. We validate this prediction experimentally, showing that lamin-depleted cells are more likely to exhibit nuclear rupture. Overall, our framework presents opportunities to predict nuclear mechanoadaptation to different microenvironments.

biophysics↗

bioRxiv2026

Potassium-Selective Nanoelectrode Arrays for Single-Cell Profiling of human iPSC-Derived Cardiomyocytes

Potassium ion (K) dynamics are central to cardiac electrophysiology, with early disruptions in K flux often preceding arrhythmia and contractile dysfunction. However, current sensing technologies, such as patch-clamp, Microelectrode arrays (MEAs), and fluorescent indicators, either lack chemical specificity for K or are unsuitable for long-term, single-cell analysis. Conventional ion-selective electrodes (ISEs), while more selective, are limited by bulk-phase design and poor spatial resolution. To address these limitations, we present KINESIS (K-Ion Nano-Electrode Selective Interface System), a nanofabricated, cell-compliant platform that enables direct, label-free potentiometric measurement of K gradients with subcellular precision. KINESIS features high-aspect-ratio nanopillars coated with a valinomycin-based K recognition membrane, forming a stable, non-invasive interface with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This architecture allows localized, Nernstian sensing of K efflux or depletion without disrupting cell membranes. Pharmacological validation shows distinct potential shifts in response to caffeine and ouabain. KINESIS thus offers a highly selective, spatially resolved approach for studying K handling in cardiotoxicity screening and patient-specific disease modeling.

pharmacology and toxicology↗

bioRxiv2024

Nanoscale curvature of the plasma membrane regulates mechanoadaptation through nuclear deformation and rupture

Nuclear translocation of the transcription regulatory proteins YAP and TAZ is a critical readout of cellular mechanotransduction. Recent experiments have demonstrated that cells on substrates with well-defined nanotopographies demonstrate mechanoadaptation through a multitude of effects - increased integrin endocytosis as a function of nanopillar curvature, increased local actin assembly on nanopillars but decreased global cytoskeletal stiffness, and enhanced nuclear deformation. How do cells respond to local nanotopo-graphical cues and integrate their responses across multiple length scales? This question is addressed using a biophysical model that incorporates plasma membrane (PM) curvature-dependent endocytosis, PM curvature-sensitive actin assembly, and stretch-induced opening of nuclear pore complexes (NPCs) in the nuclear envelope (NE). This model recapitulates lower levels of global cytoskeletal assembly on nanopillar substrates, which can be partially compensated for by local actin assembly and NE indentation, leading to enhanced YAP/TAZ transport through stretched NPCs. Using cell shapes informed by electron micrographs and fluorescence images, the model predicts lamin A and F-actin localization around nanopillars, in good agreement with experimental measurements. Finally, simulations predict nuclear accumulation of YAP/TAZ following rupture of the NE and this is validated by experiments. Overall, this study indicates that nanotopography tunes mechanoadaptation through both positive and negative feedback on mechanotransduction. Table of Contents O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=185 SRC="FIGDIR/small/619165v2_ufig1.gif" ALT="Figure 1"> View larger version (84K): org.highwire.dtl.DTLVardef@ec6d5aorg.highwire.dtl.DTLVardef@1ff6ec2org.highwire.dtl.DTLVardef@c09f46org.highwire.dtl.DTLVardef@18df50_HPS_FORMAT_FIGEXP M_FIG C_FIG This study uses experiments and biophysical modeling to examine the response and adaptation of cells to nanoscale topography of surfaces. It is shown that cytoskeletal assembly and nuclear localization of transcription regulatory factors such as YAP/TAZ can be tuned by nanoscale membrane curvature and nuclear deformation and rupture due to substrate nanotopography.

biophysics↗

bioRxiv2024

Engineered Nanotopographies Induce Transient Openings in the Nuclear Membrane

Materials with engineered nano-scale surface topographies, such as nanopillars, nanoneedles, and nanowires, mimic natural structures like viral spike proteins, enabling them to bypass biological barriers like the plasma membrane. These properties have led to applications in nanoelectronics for intracellular sensing and drug delivery platforms, some of which are already in clinical trials. Here, we present evidence that nanotopographic materials can induce transient openings in the nuclear membranes of various cell types without penetrating the cells, breaching the nucleo-cytoplasmic barrier and allowing uncontrolled molecular exchange across the nuclear membrane. These openings, induced by nanoscale curvature, are temporary and repaired through ESCRT-mediated mechanisms. Our findings suggest a potential for nano topographic materials for direct nuclear sensing and delivery, holding promise for improving the delivery, efficiency, and safety of therapeutic agents to the nucleus.

bioengineering↗

bioRxiv2023

Engineering cell and nuclear morphology on nano topography by contact-free protein micropatterning

Platforms with nanoscale topography have recently become powerful tools in cellular biophysics and bioengineering. Recent studies have shown that nanotopography affects various cellular processes like adhesion and endocytosis, as well as physical properties such as cell shape. To engineer nanopillars more effectively for biomedical applications, it is crucial to gain better control and understanding of how nanopillars affect cell and nuclear physical properties, such as shape and spreading area, and impact cellular processes like endocytosis and adhesion. In this study, we utilized a laser-assisted micropatterning technique to manipulate the 2D architectures of cells on 3D nanopillar platforms. We performed a comprehensive analysis of cellular and nuclear morphology and deformation on both nanopillar and flat substrates. Our findings demonstrate precise engineering of cellular architectures through 2D micropatterning on nanopillar platforms. We show that the coupling between nuclear and cell shape is disrupted on nanopillar surfaces compared to flat surfaces. Furthermore, we discovered that cell elongation on nanopillars enhances nanopillar-induced endocytosis. These results have significant implications for various biomedical applications of nanopillars, including drug delivery, drug screening, intracellular electrophysiology, and biosensing. We believe our platform serves as a versatile tool for further explorations, facilitating investigations into the interplay between cell physical properties and alterations in cellular processes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/543791v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1b3a13dorg.highwire.dtl.DTLVardef@1edbdaorg.highwire.dtl.DTLVardef@1f3e40corg.highwire.dtl.DTLVardef@100d6fc_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2018

The effect of susceptible and resistant potato cultivars on bacterial communities in the tuberosphere of potato in soil suppressive or conducive to common scab disease

Connections between the structure of bacterial communities in suppressive soils and potato resistance to common scab (CS) are not well understood. In this study, one resistant and one susceptible cultivar were grown in a conducive and suppressive field to assess cultivar resistance x soil suppressiveness interactions. The resistant cultivar had a higher Mg content in periderm compare to susceptible cultivar, while suppressive soil had lower pH (5.3 vs 5.9), N, C, P, Ca contents but higher Fe and S compared with the conducive soil. Bacteria and actinobacteria numbers were higher in the conducive soil. Copy numbers of txtB gene (coding for a pathogenicity determinant) were similar in both soils but were higher in the conducive soil (for periderm samples) and in the susceptible cultivar (for conducive soil samples). Taxonomic microarray analysis and Illumina sequencing of 16S rRNA genes amplicon showed that bacterial community differed between resistant vs susceptible cultivar and to a lesser extend between suppressive vs conducive soil. Bacteria participating in soil suppression belonged to Pseudomonadaceae, Bradyrhizobiaceae, Acetobacteraceae and Paenibacillaceae, while resistant cultivars selected a bacterial community resembling that of the suppressive soil, which was enriched in Nitrospirae and Acidobacteria. Thus, the analysis of soil suppressivenessxcultivar resistance interactions enabled to gain new insight to CS control in the field.\n\nIMPORTANCEIt was demonstrated that potato cultivars susceptible and resistant to common scab select differing bacterial community and above that this trait is further modified in suppressive and conducive soil. Common scab severity was diminished by either resistant cultivar or suppressive soil but without additive effect between them. Out of the two factors, potato cultivar had a more significant influence on tuberosphere bacterial community composition than soil. Results highlighted the usefulness of both cultivar resistance and soil suppressiveness traits in understanding and managing disease control of crops.

microbiology↗