Adherent cells undergo rate-softening mediated by actomyosin kinetics Friday, July 25, 2025 Emerging studies suggest that a wide range of chronic diseases can be linked to prior physical trauma and, in some cases, to the supraphysiological deformation rates experienced by cells during injury. However, the mechanical behavior of cells during these deformations is poorly understood. Here, we studied the strain rate dependent mechanics of vascular smooth muscle cells over rates spanning five orders of magnitude, from physiological to supraphysiological. We find that cells deformed at increasing rates undergo substantial rate-softening in tension but have no rate-dependence when returned to zero strain. Read more
Excitation and mechanical contraction of a 3D cardiomyocyte model Friday, July 25, 2025 Cardiomyocyte ultrastructure and pathological disruptions, such as myofibrillar disarray and mitochondrial disorganization, are important determinants of contractile function and dysfunction. Our previous model simulation assumed idealized periodicity and symmetry of cardiomyocyte structures limiting their ability to replicate pathological abnormalities. Utilizing image-based modeling, here we extend previous simulations by incorporating realistic 3-D structures based on mouse cardiomyocyte images from serial block-face scanning electron microscopy (SBEM). Read more
Transmembrane coupling drives the growth of liquid-like protein condensates Wednesday, July 23, 2025 Timely and precise assembly of protein complexes on membrane surfaces is essential to the physiology of living cells. Recently, protein phase separation has been observed at cellular membranes, suggesting it may play a role in the assembly of protein complexes. Inspired by these findings, we observed that two-dimensional protein condensates on one side of a planar suspended membrane spontaneously colocalized with those on the opposite side. How might this phenomenon contribute to the assembly of stable transmembrane complexes? To address this question, we examined the diffusion and growth of two-dimensional protein condensates on both sides of membranes. Read more
Ion-Mediated Effects of Glycosylation on the Disordered Mucin Domain: Insights from Coarse-Grained Simulations Tuesday, July 22, 2025 Mucins are essential glycoproteins that form the backbone of mucus, a hydrogel protecting epithelial surfaces throughout the body. Their biophysical properties are governed by the densely glycosylated and highly disordered proline-threonine-serine (PTS) mucin domain, which becomes negatively charged by the addition of terminal sialic acid and sulfate groups to its glycans. The properties of mucins are further modulated by their interactions with cations, particularly sodium and calcium, which influence mucus expansion and viscoelasticity. Read more
Crumbs2 acts as a dynamic cellular sensor triggering stable podocyte cell-matrix anchorage. Tuesday, July 22, 2025 Mammalian crumbs proteins (CRB) 2 and 3 are expressed in the kidney, with CRB2 mainly found within podocytes. Here, we focused on the function of CRB2 in podocytes. We investigated the CRB2/CRB3A membrane dynamics at the podocyte-podocyte contact interface in a cell culture model. Traction force microscopy was employed to clarify whether the homophilic CRB2 interactions occur in cis or trans. Live-cell imaging revealed the effects of CRB2 and CRB3A expression on cell migration from the single cell level to large cellular networks at long space and time scales. Read more
The Membrane Properties Determine Protein Function – A New Aspect of Allosteric Modulation Tuesday, July 22, 2025 Read more
Collagen as a stress test and a tool for improvement of Glycine and Proline conformations in biomolecular force fields Tuesday, July 22, 2025 Read more
3D multiscale shape analysis of nuclei and in-vivo elastic stress sensors allows force inference Tuesday, July 22, 2025 The measurement of stresses and forces at the tissue level has proven to be an indispensable tool for the understanding of complex biological phenomena such as cancer invasion, embryo development or wound healing. One of the most versatile tools for force inference at the cell and tissue level are elastic force sensors, whose biocompatibility and tunable material properties make them suitable for many different experimental scenarios. The evaluation of those forces, however, is still a bottleneck due to the numerical methods seen in literature until now, which are usually slow and render low experimental yield. Read more
Role of Dynamical Instability in QT Interval Variability and Early Afterdepolarization Propensity Monday, July 21, 2025 Beat-to-beat variability of the QT interval (QTV) is a well-established marker of cardiac health, with increased QTV (> 5 ms) often associated with a higher risk of arrhythmias. However, the underlying mechanisms contributing to this phenomenon remain poorly understood. Recently, we showed that cardiac instability is a major cause of QTV. Early afterdepolarizations (EADs) are abnormal electrical oscillations that occur during the plateau phase of the cardiac action potential (AP), often arising when the membrane potential becomes unstable. Read more
Allometric cell spreading and the geometrical control of focal adhesion collective organization Monday, July 21, 2025 Focal adhesions are protein complexes that transmit actin cytoskeleton forces to the extracellular matrix and serve as signaling hubs that regulate cell physiology. While their growth is achieved through a local force-dependent process, the requirement of sustaining stress at the cell scale suggests a global regulation of the collective organization of focal adhesions. To investigate evidence of such large-scale regulation, we compared changes in cell shape and the organization of focal adhesion-like structures during the early spreading of fibroblasts either on a two-dimensional substrate or confined between two parallel plates, and for cells of different volumes. Read more
Comparative Analysis of the Bending Modulus for Phosphatidylcholine, Phosphatidylethanolamine, and Sphingomyelin Membranes Based on Coarse-Grained Molecular Dynamics Simulations Wednesday, July 16, 2025 Bilayer membranes are essential biological structures with complex and largely unexplored mechanical properties. Using coarse-grained molecular dynamics simulations, we evaluated the bending modulus across diverse lipid compositions, including phosphatidylcholine (PC), phosphatidylethanolamine (PE), and sphingomyelin (SM). Three computational techniques were employed to calculate the bending modulus from thermal fluctuations of the simulated bilayers: the Fourier transform of the lipid height function (q−4 fitting), Bedeaux-Weeks Density Correlation Functions (BW-DCF) method, and Real Space Fluctuations (RSF). Read more