Enzyme-Regulated Non-Thermal Fluctuations Enhance Ligand Diffusion and Receptor-Mediated Endocytosis.

Active enzymes during catalyzing chemical reactions, have been found to generate significant mechanical fluctuations, which can influence the dynamics of their surroundings. These phenomena open new avenues for controlling mass transport in complex and dynamically inhomogeneous environments through localized chemical reactions. To explore this potential, we studied the uptake of transferrin molecules in retinal pigment epithelium (RPE) cells via clathrin-mediated endocytosis.

Free energy calculations for membrane morphological transformations and insights to physical biology and oncology.

In this chapter, we aim to bridge basic molecular and cellular principles surrounding membrane curvature generation with rewiring of cellular signals in cancer through multiscale models. We describe a general framework that integrates signaling with other cellular functions like trafficking, cell-cell and cell-matrix adhesion, and motility. The guiding question in our approach is: how does a physical change in cell membrane configuration caused by external stimuli (including those by the extracellular microenvironment) alter trafficking, signaling and subsequent cell fate? We answer this question by constructing a modeling framework based on stochastic spatial continuum models of cell membrane deformations.

Asymmetric crowders and membrane morphology at the nexus of intracellular trafficking and oncology.

A definitive understanding of the interplay between protein binding/migration and membrane curvature evolution is emerging but needs further study. The mechanisms defining such phenomena are critical to intracellular transport and trafficking of proteins. Among trafficking modalities, exosomes have drawn attention in cancer research as these nano-sized naturally occurring vehicles are implicated in intercellular communication in the tumor microenvironment, suppressing anti-tumor immunity and preparing the metastatic niche for progression.

Data driven and biophysical insights into the regulation of trafficking vesicles by extracellular matrix stiffness.

Biomechanical signals from remodeled extracellular matrix (ECM) promote tumor progression. Here, we show that cell-matrix and cell-cell communication may be inherently linked and tuned through mechanisms of mechanosensitive biogenesis of trafficking vesicles. Pan-cancer analysis of cancer cells' mechanical properties (focusing primarily on cell stiffness) on substrates of varied stiffness and composition elucidated a heterogeneous cellular response to mechanical stimuli.

Quantification of Curvature Sensing Behavior of Curvature-Inducing Proteins on Model Wavy Substrates.

Curvature-inducing proteins are involved in a variety of membrane remodeling processes in the cell. Several in vitro experiments have quantified the curvature sensing behavior of these proteins in model lipid systems. One such system consists of a membrane bilayer laid atop a wavy substrate (Hsieh in Langmuir 28:12838-12843, 2012).