Demonstrating Self-Assembly of Intracellular Condensates from Mixtures of Shared Components with Molecular Dynamics Simulation

Abstract

Liquid-liquid phase separation is a thermodynamically driven phenomenon that has been suggested as an explanation for the formation of protein intracellular condensates. Understanding the dynamics of these condensates is a question of interest given the increasing evidence associating condensates with aging-related diseases like cancer and various neurodegenerative diseases. Complex phase behaviors have been observed in cells where multiple condensates exist in parallel and contain shared components. This senior thesis seeks to understand how a designed system of interaction potentials might enable proteins to exhibit these complex phase behaviors in cells. By conducting and analyzing molecular dynamics simulations, this research attempts to demonstrate that a simple designed system of interaction potentials can provide conditions that allow for the growth of multiple condensates with distinct compositions from the same heterogenous mixture. The paper also explores how variations in interaction potential effect phase separation and how these variations effect condensate composition and growth. Future work should continue to explore the effects of different variations to interaction potentials like cutoff distance and particle size on condensate composition and attempt to encode greater numbers of condensates in more diverse mixtures of particles.