Biology subjects

Elson, E. L.

Publications and source records attributed to Elson, E. L..

8 recordsLinked to original sources

bioRxiv2026

Synaptopodin enables directional mechanoadaptation of integrin-based adhesions

The attachment of cells to their substrate through adhesion complexes is fundamental to tissue architecture and function. These adhesions are inherently optimized to resist shear forces parallel to the substrate, yet certain specialized cells must also withstand substantial perpendicular forces. How cells adapt their adhesion machinery to resist forces in different directions has remained unclear. In the kidney, podocytes experience perpendicular forces from pressurized filtrate flow while maintaining attachment to the glomerular basement membrane through integrin-based adhesions. Here we show that synaptopodin converts adhesions from shear-resistant to perpendicular force-resistant structures through coordinated reorganization of the actin cytoskeleton and adhesion complexes. Using an inertial force application system, we demonstrate that synaptopodin triggers force-dependent redistribution of {beta}1-integrin to the cell periphery specifically in response to perpendicular loading, while synaptopodin-deficient cells lack this directional adaptation and detach. This mechanism operates in multiple cell types and is physiologically essential: synaptopodin-null mice subjected to elevated glomerular pressure develop significant proteinuria and podocyte foot process effacement. These findings reveal a molecular basis for directional mechanoadaptation, whereby a single protein enables cells to reconfigure their adhesion architecture in response to the direction of applied force.

biophysics↗

bioRxiv2025

3D-printing-assisted, microfabricated devices reveal hierarchical and temporal mechanosensing in high-density fibroblast culture

Understanding how cells integrate mechanical forces across multiple directions, length scales, and timescales remains a fundamental challenge in mechanobiology. Deciphering how cells integrate this information is particularly important in the context of wound healing, where the timing and duration of the fibroblast-to-myofibroblast transition can determine healing outcomes. Here, we discovered that fibroblasts in engineered tissues respond to directional anisotropy in stress through a hierarchical temporal cascade, with individual cell elongation (24 hr) preceding collective alignment (40 hr), which then drives -smooth muscle actin expression and myofibroblast transition (96h). To enable this discovery, we developed a modified hydrogel-assisted stereolithographic elastomer (HASTE) prototyping platform to incorporate a detergent that improves wettability of template agar hydrogels by poly(dimethylsiloxane) elastomer. HASTE allowed rapid prototyping of intricate 3D micropost arrays that provides isotropic (8-post) versus anisotropic (4-post) boundary conditions. Fibroblasts sensed and responded to stress directionality before bulk tissue reorganization occurs. Computational modeling predicted steady-state activation patterns based on initial stress anisotropy rather than magnitude, and our experiments reveal that reaching this state requires sequential mechanosensitive processes operating across distinct timescales. This temporal hierarchy persists even when extensive cell-cell contacts might be expected to mask matrix-mediated mechanical signals. Our findings demonstrate that fibroblast mechanosensing involves adaptive responses encoded through progressive cell and tissue reorganization. Results provide insight into how nanoscale mechanosensing scales up to direct tissue-level organization, with implications for understanding wound healing, understanding fibrosis, and engineering functional tissue replacements.

bioengineering↗

bioRxiv2025

Tension-Induced Stiffening of Cytoskeletal Components Regulates Cardiomyocyte Contractility

Cardiomyocytes continuously experience mechanical stimuli that regulate their contractile behavior and contribute to overall heart function. Despite the importance of mechanotransduction in cardiac physiology, the mechanisms by which cardiomyocytes integrate external mechanical cues, such as stretch and environmental stiffness, remain poorly understood. In this study, we present a combined theoretical and experimental framework to investigate how strain-induced cytoskeletal stiffening modulates cardiomyocyte contractility and force generation. Our study elucidates that regulating the mechanical tension cardiomyocytes experience in tissue--whether by modulating environmental stiffness, external stretching, or cardiac fibroblast activation--can effectively tune their contractility, with cytoskeletal strain stiffening playing a central role in this mechanotransductive response.

biophysics↗

bioRxiv2024

Critical Spacing in Cell-Matrix Mechanical Feedback Controls Tissue Condensation

Biological tissues exhibit phase transitions governed by mechanical feedback between cells and their extracellular matrix (ECM). We demonstrate through bio-chemo-mechanical modeling that this emergent behavior arises from competing physical effects: increasing matrix stiffness enhances individual cell activation while simultaneously weakening long-range mechanical communication. This competition establishes a critical cell spacing threshold (80-160 {micro}m) that precisely matches experimental observations across diverse cell types and collagen densities. Our model reveals that the critical stretch ratio at which fibrous networks transition from compliant to strain-stiffening governs this threshold through the formation of tension bands between neighboring cells. These tension bands create a mechanical percolation network that drives the collective phase transition in tissue behavior. Our model explains how fibrous architecture controls emergent mechanical properties in biological systems and offers insight into both the physics of fiber-reinforced composite materials under active stress, and into potential mechanical interventions for fibrotic disorders.

biophysics↗

bioRxiv2019

Fluorescence correlation spectroscopy and photon count histograms in small domains. Part I: General theory

Analysis of fluctuations arising as fluorescent particles pass through a focused laser beam has enabled quantitative characterization of molecular kinetic processes. The mathematical frameworks of both fluorescence correlation spectroscopy (FCS) and photon counting histogram (PCH) analysis, which can measure these fluctuations, assume an infinite Gaussian beam, which prevents their application to particles within domains bounded at the nanoscale. We therefore derived general forms of FCS and PCH for bounded systems. The finite domain form of FCS differs from the classical form in its boundary and initial conditions and requires development of a new Fourier space solution for fitting data. Our finite-domain FCS predicts simulated data accurately and reduces to a previous model for the special case of molecules confined by two boundaries under Gaussian beams. Our approach enables estimation of the concentration of diffusing fluorophores within a finite domain for the first time. The method opens the possibility of quantification of kinetics in several systems for which this has never been possible, including in the one-dimensional lipid tubules discussed in Part 2 of this paper. Statement of SignificanceMethods based on fluorescence measurements of molecular concentration fluctuations, including Fluorescence Correlation Spectroscopy and Photon Count Histogram analysis, are widely used to determine rates of diffusion, chemical reaction and sizes of molecular aggregates. Typically, the range over which the molecules can diffuse is large compared to the size of the focused laser beam that excites the fluorescence. This work extends these measurements to systems that are comparable in size to the excitation laser beam. This extends the application of these methods to very small samples such as the interior of bacterial cells or the diffusion of molecules along individual macromolecules such as DNA.

biophysics↗

bioRxiv2019

MCH4 is a multicopy suppressor of glycine toxicity in Saccharomyces cerevisiae

Saccharomyces cerevisiae can either import amino acids from the surrounding or synthesize inside the cell, and both processes are tightly regulated. Disruption of such regulation can result in amino acid toxicity to the cell through mechanisms that are poorly understood. In this study we make use of a mutant strain with deregulated general amino acid permease gene whose growth is inhibited by low concentrations of several amino acids. We carry out multicopy suppression screen with several toxic amino acids and identify MCH4 as a gene that suppresses inhibitory effects of glycine. We find that expression of MCH4 is regulated by osmotic shock but not other kinds of stress. These findings are discussed in the context of possible mechanisms of amino acid toxicity.

biochemistry↗

bioRxiv2018

Atomic force microscopy of phase separation on ruptured, giant unilamellar vesicles

Giant unilamellar vesicles (GUVs) and supported lipid bilayers (SLBs) are synthetic model systems widely used in biophysical studies of lipid membranes. Phase separation behaviors of lipid species in these two model systems differ due to the lipid-substrate interactions that are present only for SLBs. Therefore, GUVs are believed to resemble natural cell membranes more closely, and a very large body of literature focuses on applying nano-characterization techniques to quantify phase separation on GUVs. However, one important technique, atomic force microscopy (AFM), has not yet been used successfully to study phase separation on GUVs. In the present study, we report that in binary systems, certain phase domains on GUVs retain their original shapes and patterns after the GUVs rupture on glass surfaces. This enabled AFM experiments on phase domains from binary GUVs containing 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) and either 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). These DLPC/DSPC and DLPC/DPPC GUVs both presented two different gel phases, one of which (bright phase) included a relatively high concentration of DiI-C20 but excluded Bodipy-HPC, and the other of which (dark phase) excluded both probes. The bright phases are of interest because they seem to stabilize dark phases against coalescence. Results suggested that the gel phases labeled by DiI-C20 in the DLPC/DSPC membrane, which surround the dark gel phase, is an extra layer of membrane, indicating a highly curved structure that might stabilize the interior dark domains. This phenomenon was not found in the DLPC/DPPC membrane. These results show the utility of AFM on collapsed GUVs, and suggest a possible mechanism for stabilization of lipid domains.

biochemistry↗

bioRxiv2017

FCS In Closed Systems And Application For Membrane Nanotubes

In the present study, we developed the fluorescence correlation spectroscopy theory for closed systems with either periodic or reflective boundaries. The illumination could be any arbitrary function. We tested our theory with simulated data of both boundary conditions. We also tested the theory with experimental data of membrane nanotubes, whose circular direction is a closed system. The result shows that the correlation function for nanotubes falls between 1D and 2D diffusion model. The fitting with our model gives an accurate recovery of the diffusion time and nanotube radius. We also give some examples of single molecule experiments for which our theory can be potentially useful.

biophysics↗