Cell membranes act as semi-permeable barriers, often restricting the entry of large or hydrophilic molecules. Nonetheless, certain amphiphilic molecules, like antimicrobial and cell-penetrating peptides, can cross these barriers. In this study, we demonstrate that specific properties of transmembrane proteins/peptides can enhance membrane permeation of amphiphilic peptides. Using coarse-grained molecular dynamics with free energy calculations, we identify key translocation-enhancing attributes of transmembrane proteins/peptides: a continuous hydrophilic patch, charged residues preferably in th ..read more

Controlling mesenchymal stem cells (MSCs) differentiation remains a critical challenge in their therapeutic application. Numerous biophysical and mechanical stimuli influence stem cell fate, however, their relative efficacy and specificity in mechanically directed differentiation remain unclear. Yes-associated protein (YAP) is one key mechanosensitive protein that controls MSC differentiation. Previous studies have related nuclear mechanics with YAP activity, but we still lack an understanding of what nuclear deformation specifically regulates YAP, and its relationship with mechanical stimuli ..read more

Disordered proteins are conformationally flexible proteins that are biologically important and have been implicated in devastating diseases such as Alzheimer’s and cancer. Unlike stably-folded structured proteins, disordered proteins sample a range of different conformations that needs to be accounted for. Here, we treat disordered proteins as polymer chains, and compute a dimensionless quantity called instantaneous shape ratio ( is end-to-end distance and ..read more

R) mediates Ca release in many cell types and is pivotal to a wide range of cellular processes. High resolution cryo-electron microscopy (Cryo-EM) studies have provided new structural details of IP R1), showing that channel function is determined by the movement of various domains within and between each of its four subunits. Channel properties are regulated by ligands, such as Ca and IP3, which bind at specific sites and control the interactions between these domains ..read more

R) mediates Ca release in many cell types and is pivotal to a wide range of cellular processes. High resolution cryo-electron microscopy (Cryo-EM) studies have provided new structural details of IP R1), showing that channel function is determined by the movement of various domains within and between each of its four subunits. Channel properties are regulated by ligands, such as Ca and IP3, which bind at specific sites and control the interactions between these domains ..read more

Red blood cells (RBCs) are vital for transporting oxygen from the lungs to the body’s tissues through the intricate circulatory system. They achieve this by binding and releasing oxygen molecules to the abundant hemoglobin within their cytosol. The volume of RBCs affects the amount of oxygen they can carry, yet whether this volume is optimal for transporting oxygen through the circulatory system remains an open question. This study explores, through high-fidelity numerical simulations, the impact of RBC volume on advectve oxygen transport efficiency through arterioles which form the area of gr ..read more

Red blood cells (RBCs) are vital for transporting oxygen from the lungs to the body’s tissues through the intricate circulatory system. They achieve this by binding and releasing oxygen molecules to the abundant hemoglobin within their cytosol. The volume of RBCs affects the amount of oxygen they can carry, yet whether this volume is optimal for transporting oxygen through the circulatory system remains an open question. This study explores, through high-fidelity numerical simulations, the impact of RBC volume on advectve oxygen transport efficiency through arterioles which form the area of gr ..read more

Voltage-gated potassium channels are critical in modulating cellular excitability, with Slo (slowpoke) channels forming a unique family characterized by their large conductance and dual regulation by electrical signals and intracellular messengers. Despite their structural and evolutionary similarities, Slo1 and Slo3 channels exhibit significant differences in their voltage-gating properties. This study investigates the molecular determinants that differentiate the voltage-gating properties of human Slo1 and mouse Slo3 channels ..read more

Early embryogenesis of the nematode progresses in an autonomous fashion within a protective chitin eggshell. Cell division timing and the subsequent, mechanically guided positioning of cells is virtually invariant between individuals, especially before gastrulation. Here, we have challenged this stereotypical developmental program in early stages by mechanically perturbing the embryo, without breaking its eggshell. Compressing embryos to about 2/3 of their unperturbed diameter only resulted in markedly slower cell divisions ..read more

Lytic polysaccharides monooxygenases (LPMOs) catalyze a reaction that is crucial for the biological decomposition of various biopolymers and for the industrial conversion of plant biomass. Despite the importance of LPMOs, the exact molecular-level nature of the reaction mechanism is still debated today. Here, we investigated the pH dependent conformation of a second sphere histidine (His) that we call the “stacking histidine”, which is conserved in fungal AA9 LPMOs, and is speculated to assist catalysis in several of the LPMO reaction pathways ..read more