Lipid Demixing Reduces Energy Barriers for High Curvature Vesicle Budding Friday, December 13, 2024 Under standard physiological conditions, budding relies on asymmetries, including differences in leaflet composition, area, and osmotic conditions, and involves large curvature changes in nanoscale lipid vesicles. So far, the combined impact of asymmetry and high curvatures on budding has remained unknown. Here, using continuum elastic theory, the budding pathway is detailed under realistic conditions. The model enables a quantitative description of the budding process and the budded state of both ideally and non-ideally mixed lipid nanoscale vesicles. Read more
Assembly landscape of the complete B-repeat superdomain from Staphylococcus epidermidis strain 1457 Wednesday, December 11, 2024 The accumulation-associated protein (Aap) is the primary determinant of Staphylococcus epidermidis device-related infections. The B-repeat superdomain is responsible for intercellular adhesion that leads to the development of biofilms occurring in such infections. It was recently demonstrated that Zn-induced B-repeat assembly leads to formation of functional amyloid fibrils, which offer strength and stability to the biofilm. Rigorous biophysical studies of Aap B-repeats from S. epidermidis strain RP62A revealed Zn-induced assembly into stable, reversible dimers and tetramers, prior to aggregation into amyloid fibrils. Read more
Fine-tuning of Fgf8 morphogen gradient by heparan sulfate proteoglycans in the extracellular matrix Wednesday, December 11, 2024 Embryonic development is orchestrated by the action of morphogens, which spread out from a local source and activate, in a field of target cells, different cellular programs based on their concentration gradient. Fibroblast growth factor 8 (Fgf8) is a morphogen with important functions in embryonic organizing centers. It forms a gradient in the extracellular space by free diffusion, interaction with the extracellular matrix (ECM) and receptor-mediated endocytosis. However, morphogen gradient regulation by ECM is still poorly understood. Read more
Proton reactions: From basic science to biomedical applications Friday, December 6, 2024 Proton transfer is ubiquitous in biology. Specialized proteins—channels, pumps, and antiporters—transfer protons across cell membranes to establish proton electrochemical gradients needed to power energetically costly chemical reactions and perform myriad other tasks. Other proteins, enzymes, transfer protons locally during the chemical reaction they catalyze. How such proton transfers occur is a fundamental issue with implications for biomedical and biotechnological research. The Biophysical Journal special issue “Proton reactions: From basic science to biomedical applications” arises from the Biophysical Society conference that took place in Tahoe, California, in August 2023. Read more
TGF-β2 enhances nanoscale cortex stiffness via condensation of cytoskeleton-focal adhesion plaque Friday, December 6, 2024 SIGNIFICANCE: Cell cortex stiffness affects the health of vertebrate cells and varies with the progression of inflammatory diseases such as osteoarthritis (OA). The various cytokines, such as inflammatory factors, growth factors, and chemokines, accompany the deterioration of inflammatory OA and play an important role in cortex stiffness of chondrocytes. In the current study, we report the role of TGF-β2 on the nanoscale cortex stiffness of chondrocytes by using AFM and its triggering processes including cell protrusion formation, actin microfilament bundling and focal adhesion colocalization. These results are beneficial for revealing the association between cell cortex stiffness and disease occurrence and development. Read more
Roles for PKC signaling in chromaffin cell exocytosis Thursday, December 5, 2024 Chromaffin cells of the adrenal medulla have an important role in the sympathetic stress response. They secrete catecholamines and other hormones into the bloodstream upon stimulation by the neurotransmitter pituitary adenylate cyclase-activating polypeptide (PACAP). PACAP causes a long-lasting and robust secretory response from chromaffin cells. However, the cellular mechanisms by which PACAP causes secretion remain unclear. Our previous work showed that the secretory response to PACAP relies on signaling through phospholipase C ε (PLCε). Read more
Low-side and multi-tone suppression in the base of the gerbil cochlea Thursday, December 5, 2024 The cochlea’s mechanical response to sound stimulation is nonlinear, likely due to saturation of the mechano-electric transduction current that is part of an electromechanical feedback loop. The ability of a second tone or tones to reduce the response to a probe tone is one manifestation of nonlinearity, termed suppression. Using optical coherence tomography to measure motion within the organ of Corti, regional motion variations have been observed. Here, we report on the suppression that occurs within the organ of Corti when a high sound level, low frequency suppressor tone was delivered along with a sweep of discreet single-tones. Read more
Empirical methods that provide physical descriptions of dynamic cellular processes Thursday, December 5, 2024 We review empirical methods that can be used to provide physical descriptions of dynamic cellular processes during development and disease. Our focus will be non-spatial descriptions and the inference of underlying interaction networks including cell state lineages, gene regulatory networks, and molecular interactions in living cells. Our overarching questions are: How much can we learn from just observing? To what degree is it possible to infer causal and/or precise mathematical relationships from observations? We restrict ourselves to datasets arising from only observations, or experiments in which minimal perturbations have taken place to facilitate observation of the systems as they naturally occur. Read more
Energy-based bond graph models of glucose transport with SLC transporters Thursday, December 5, 2024 SIGNIFICANCE Physiological systems typically involve coupled mechanical, electrical and chemical processes, with energy acting as a universal currency across these domains. We propose a new visual representation for all components of these processes using bond graphs. Bringing all physical processes under one consistent framework greatly simplifies the task of understanding multiscale physiological processes. This energy-based framework, which is the 0D version of a more general 3D port-Hamiltonian theory, can be used to model all lumped parameter physiological processes. A small number of bond graph templates can be used to model all members of the large SLC transporter family, and reduced thermodynamically consistent steady-state flux models provide a useful simplification for many situations. Glucose transport is chosen here to illustrate the bond graph approach because it represents the first step in cell metabolic processes, where energy conservation needs to be a fundamental characteristic of quantitative models. Our future work on cell metabolism will build on the foundation established here. Read more
Full identification of a growing and branching network’s spatio-temporal structures. Thursday, December 5, 2024 Experimentally monitoring the kinematics of branching network growth is a tricky task, given the complexity of the structures generated in three dimensions. One option is to drive the network in such a way as to obtain two-dimensional growth, enabling a collection of independent images to be obtained. The density of the network generates ambiguous structures, such as overlaps and meetings, which hinder the reconstruction of the chronology of connections. In this paper, we propose a general method for global network reconstruction. Read more
Stomatocyte-Discocyte-Echinocyte Transformations of Erythrocyte Modulated by Membrane-Cytoskeleton Mechanical Properties Thursday, December 5, 2024 Stomatocyte-discocyte-echinocyte (SDE) transformations in human red blood cells (RBCs) have significant influences on blood dynamics and related disorders. The mechanical properties of the RBC membrane, such as shear modulus and bending elasticity, play crucial roles in determining RBC shapes. Recent biophysical findings reveal that building a comprehensive model capable of describing SDE shape transformations is a challenging problem. Based on dissipative particle dynamics, this study develops a two-component RBC model considering the detachment between the lipid bilayer and cytoskeleton, as well as the cytoskeletal reorganization during echinocyte formation. Read more