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The parasitic unicellular microswimmer Trypanosoma brucei is the causative agent for severe diseases in humans and cattle. Trypanosomes have a complex life cycle with the best characterized stages being the bloodstream form (BSF) in the vascular system of the mammalian host and the procyclic form (PCF) in the gut of the tsetse fly vector. Morphologically, PCF and BSF trypanosomes appear very similar, being propelled by a single flagellum that is wrapped around the spindle-shaped cell body. Despite this similarity, we show here that PCF and BSF trypanosomes have significantly different motility patterns and are also very different in their sensitivity to the ambient temperature.

Podosomes are actin-rich protrusions in immune cells that function as mechanosensors, helping cells to sense the extracellular matrix (ECM). These structures exhibit spontaneous oscillations, driven by a balance between actin-driven protrusion and myosin-mediated contraction. While podosome responses to matrix stiffness are well-studied, their behavior in mechanically pre-stretched ECMs—common in both physiological and pathological contexts—remains unclear. In this study, we developed a novel chemo-mechanical model that integrates intracellular force generation with contact mechanics at the podosome-ECM interface.

Excessive production of reactive oxygen species (ROS) in cells results in oxidative stress, which can promote lipid oxidation in cellular membranes. This oxidation of membrane lipids accompanies various diseases and can even result in cell death through processes such as ferroptosis. The complex compositions and diverse morphologies of cellular membranes make understanding the mechanisms of lipid oxidation challenging, especially when attempting to investigate membrane composition and curvature simultaneously.

It is a great pleasure to share with you a special issue of Biophysical Journal dedicated to Erich Sackmann (Figure 1), who was a trailblazer in the field of cell biophysics. Sackmann, Professor Emeritus of Excellence in the Department of Physics at the Technical University Munich in Germany, passed away in May 2024 at the age of 89, leaving behind a large community of biophysicists, whom he personally taught and mentored or who were inspired by his teachings and scientific endeavors. To celebrate his remarkable and creative scientific life, we are happy to present you this special issue, which reflects Sackmann’s deep interest in understanding the physics of the living cell, ranging from mechanics to thermodynamics, from molecules to a single cell to cell collectives, from experiments to theory.

Interactions between nucleic acids and ligands are vital for gene regulation and therapy development, yet accurate modeling is hindered by shallow, flexible pockets and conformational changes. Existing docking approaches typically assume that both ligands and nucleic acids are rigid, which results in sampling pools that lack near-native conformations and makes it more challenging for scoring functions to distinguish correct poses from decoys. We introduce ZHMolLigGraph, a two-stage graph-based deep learning framework that explicitly models ligand flexibility.

Understanding the mechanical properties of animal cells is essential for fundamental biological processes. Two key quantities for these properties are the effective stiffness of the cell (E) and intracellular pressure (P). Their combined influence is significant for understanding cell deformation due to external forces. However, there is no general method to simultaneously quantify E and P in animal cells. In this study, we used atomic force microscopy (AFM) to obtain topographic images and force-indentation curves of adherent animal cells, which were then analyzed by applying elastic shell theory (EST).

The transport of individual entities through interconnected structures is a process of practical relevance both in biology and technology. Examples are given by diffusive dynamics of molecules in porous structures. In soft environments, this transport can be strongly influenced by fluctuations of the porous structure itself. Here, we focus on triply periodic membrane structures found both in cell organelles and in synthetic amphiphilic systems. We theoretically study the effect of a complex three-dimensional fluctuating environment on the diffusive motion of a test object, using a phase field approach.

Recent advances in connectomics have been led by high-resolution reconstruction of large volumes of neural tissues using electron microscopy (EM), providing unprecedented insights into brain structure and function. Dendritic spines—dynamic protrusions on neuronal dendrites—play crucial roles in synaptic plasticity, influencing learning, memory, and various neurological disorders. However, current spine analysis methods often rely on manual annotation of subcellular features, limiting their ability to handle the complexity of spines in dense dendritic networks.

Contradictory experimental reports on the relationship between efficiency and stimulation frequency have hindered mechanistic understanding of how neural activity is converted into mechanical work during muscle contraction. To resolve this issue, we develop a biophysical model that integrates calcium-mediated excitation with a detailed cross-bridge cycle, enabling single-fiber simulations. Our model predicts that the emergent shortening velocity is the primary determinant of cross-bridge efficiency: efficiency peaks at an optimal velocity and declines at higher or lower velocities, while stimulation frequency plays only a secondary role.

Epithelial tissues in vivo are often subjected to the challenge of mechanical forces and osmotic shock. However, how epithelial cells prevent DNA damage and reduce aging and apoptosis in the presence of these intense external stimuli remains unclear. Here, we found a reversible perinuclear actin ring can be assembled after rapid and significant hypotonic shock or mechanical forces. Combining experiments and simulations, we demonstrate it is merely a transient response of actin network that is regulated by Ca2+-mediated actin disassembly and Arp2/3-dependent actin polymerization.

Neuronal cells are subject to large ion fluxes during synaptic transmission. Here, we find that addition of Na+ or K+ to PC12 cells to concentrations above 350 mOsm and similar to those experienced during stimulation induces neurite retraction. Retraction is mediated by the activity of Na+ and K+ channels and requires Cl- to preserve electroneutrality and does not occur with other osmolytes. Using a probe sensitive to membrane tension, we find that under basal conditions there is a difference in tension between neurites and the somas that equalize as the neurites retract.

A quantification method to study material properties of pectin enriched layers in wild type (WT) Arabidopsis thaliana leaves is proposed here. In this paper, the mechanical and adhesive properties of this layer were investigated by measuring the response of deep-needle insertion into the pectin-enriched areas of live leaf samples in WT Arabidopsis thaliana using two different conical probes. One was a commercial diamond tip with a radius of 5 μm, while the other was a sharp tungsten tip with a radius of 110 nm.