Modeling the Cellular Mechanobiology of Microparticle Formation
Abstract
In this project, funded through the PECASE mechanism, the overarching goal of the proposed research is to build quantitative and predictive computational models of microparticle formation. This research will be carried under three specific aims. Aim 1 will focus on the role of membrane mechanics and lipid asymmetry in the formation of microparticles. Our approaches in this aim include coarse-grained simulations of lipid bilayers accounting for the composition heterogeneity and continuum mechanics approaches for membrane curvature generation and bending during microparticle formation. Both these efforts together will result in a multiscale model for the role of membranes in microparticle formation. Aim 2 will focus on the development of mathematical and computational models that investigate how actin and plasma membrane interactions modulate the mechanics of microvesicle formation under hyperbaric pressure. It is well-established that cells experienceincreased oxygen toxicity and oxidative stress under conditions of hyperbaric pressure and release microvesicles. However, how hyperbaric pressure affects the mechanics of the plasma membrane and actin cytoskeleton to promote the formation and release of microvesicles remains poorly understood. The development of mathematical and computational models that can predict how mechanical forces, coupled with biochemical effects can promote microvesicle formation will be a crucial aspect for gaining a quantitative understanding of these fundamental cellular processes. Finally, Aim 3 will focus on alterations tomitochondrial mechanics under hyperbaric pressure. Mitochondria perform a variety of key biological processes, including regulation of ion gradients, membrane potential, ROS generation, and heat dissipation. A recent experimental study by Dr. David Eckmanns group has shown that under simulated dive conditions, fibroblasts showed altered mitochondrial respirationrates, mitochondrial motility, and alterations to cytoskeletal dynamics and cell shape. This is one of the first controlled observations of the effect of hyperbaric pressure and the dive conditions on cellular energetics. These preliminary observations point to the fact that conditions associated with high pressure alter cellular mechanics and mitochondrial function. In this portion of the project, I will develop mathematical and computational models to probe how mechanics interfaces with cellular respiration to regulate the energy demands of cells under various dive conditions.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jun 17, 2020
- Source ID
- N000142012469
Entities
People
- Padmini Rangamani
Organizations
- Office of Naval Research
- United States Navy
- University of California, San Diego