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Building off the momentum of the Black Lives Matter movement and serving as a platform for radical reform of structural inequities, the Biophysical Society (BPS) held the President’s 2023 Black in Biophysics Symposium. The goal of this symposium was to bring to light the remarkable work of some of our Black BPS colleagues flanked by two very different cultural perspectives explaining why, in these modern times, such a spotlight is still needed. In his introduction, Bil Clemons provided data to underscore the persistent legacy of slavery, and Theanne Griffith closed the event with a moving personal testimony.

Pancratistatin (PST) and narciclasine (NRC) are natural therapeutic agents which exhibit specificity towards the mitochondria of cancerous cells and initiate apoptosis. Unlike traditional cancer therapeutic agents, PST and NRC are effective, targeted, and have limited adverse effects on neighbouring healthy, non-cancerous cells. Currently, the mechanistic pathway of action for PST and NRC remains elusive, which in part inhibits PST and NRC from becoming efficacious therapeutic alternatives. Herein, we use neutron and X-ray scattering in combination with calcein-leakage assays to characterize the effects of PST, NRC, and Tamoxifen (TAM) on a biomimetic model membrane.

The efficient permeation across the Gram-negative bacterial membrane is an important step in the overall process of antibacterial action of a molecule and the one that has posed a significant hurdle on the way towards approved antibiotics. Predicting the permeability for a large library of molecules and assessing the effect of different molecular transformations on permeation rates of a given molecule is critical to the development of effective antibiotics. We present a computational approach for obtaining estimates of molecular permeability through a porin channel in a matter of hours using a Brownian dynamics approach.

The brain cells are affected by continuous fluid shear stress that is driven by varying hydrostatic and osmotic pressure conditions, depending on the brain's pathophysiological conditions. Although all brain cells are sensitive to the subtle changes in various physicochemical factors in the microenvironment, microglia, the resident brain immune cells, exhibit the most significant morphodynamic transformation. However, little is known about the phenotypic alterations in microglia in response to changes in fluid shear stress.

Clustering of weakly interacting multivalent biomolecules underlies the formation of membrane-less compartments known as condensates. As opposed to single component (homotypic) systems, the concentration dependence of multi-component (heterotypic) condensate formation is not well understood. We previously proposed the solubility product (SP), the product of monomer concentrations in the dilute phase, as a tool for understanding the concentration dependence of multi-component systems. In the current study, we further explore the limits of the SP concept using spatial Langevin dynamics and rule-based stochastic simulations.

Wound closure is a fundamental process in many physiological and pathological processes, but the regulating effects of external force on the closure process are still unclear. Here we systematically studied the closure process of wounds of different shape under cyclic stretching. We found that the stretching amplitude and direction had significant effect on the healing speed and healing mode. For instance, there was a biphasic dependence of the healing speed on the stretching amplitude. That is, the wound closure was faster under relatively small and large amplitude, while it was slower under intermediate amplitude.

Fluorescent microscopy is the primary method to study DNA organization within cells. However the variability and low signal-to-noise commonly associated with live-cell time lapse imaging challenges quantitative measurements. In particular, obtaining quantitative or mechanistic insight often depends on the accurate tracking of fluorescent particles. Here, we present ★Track, an inference method that determines the most likely temporal tracking of replicating intracellular particles such DNA loci while accounting for missing, merged and spurious detections.

Major histocompatibility complex class II (MHC-II) plays an indispensable role in activating CD4+ T cell immune responses by presenting antigenic peptides on the cell surface for recognition by T cell receptors (TCRs). The assembly of MHC-II and antigenic peptide is therefore a prerequisite for the antigen presentation. To date, however, the atomic-level mechanism underlying the peptide-loading dynamics for MHC-II is still elusive. Here, by constructing Markov state models (MSMs) based on extensive all-atom molecular dynamics (MD) simulations, we reveal the complete peptide-loading dynamics into MHC-II for one SARS-CoV-2 S-protein-derived antigenic peptide (235ITRFQTLLALHRSYL249).

We develop a theory for inferring equilibrium transition rates from trajectories driven by a time dependent force using results from stochastic thermodynamics. Applying the Kawasaki relation to approximate the nonequilibrium distribution function in terms of the equilibrium distribution function and the excess dissipation, we formulate a nonequilibrium transition state theory to estimate the rate enhancement over the equilibrium rate due to the nonequilibrium protocol. We demonstrate the utility of our theory in examples of pulling of harmonically trapped particles in 1 and 2 dimensions, as well as a semi-flexible polymer with a reactive linker in 3 dimensions.

Cells in living organisms are subjected to mechanical strains caused by external forces like overcrowding, resulting in strong deformations that affect cell function. We study the interplay between deformation and crowding of red blood cells (RBCs) in dispersions of non-absorbing rod-like viruses. We identify a sequence of configurational transitions of RBC doublets, including configurations that can only be induced by long-ranged attraction: highly fluctuating T-shaped and face-to-face configurations at low, and doublets approaching a complete spherical configuration at high rod concentrations.

Chromosomes endure mechanical stresses throughout the cell cycle, for example resulting from the pulling of chromosomes by spindle fibers during mitosis or deformation of the nucleus during cell migration. The response to physical stress is closely related to chromosome structure and function. Micromechanical studies of mitotic chromosomes have revealed them to be remarkably extensible objects and informed early models of mitotic chromosome organization. We use a data-driven, coarse-grained polymer modeling approach to explore the relationship between the spatial organization of individual chromosomes and their emergent mechanical properties.

[FeFe] hydrogenases are enzymes that have acquired a unique capacity to synthesize or consume molecular hydrogen (H2). This function relies on a complex catalytic mechanism involving the active site and two distinct electron and proton transfer networks (EPTN) working in concert. By an analysis based on Terahertz vibrations of [FeFe] hydrogenases structure, we are able to predict and identify the existence of rate promoting vibrations (RPV) at the catalytic site and the coupling with functional residues involved in reported EPTN.