The present study addresses a specific class of transport processes inside cells, namely, those involving nanoscale (10-100 nm) entities, including cellular organelles (e.g. mitochondria, vesicles ), pathogens (e.g. viruses ) and synthetic materials (e.g. drug and gene carriers ). Transport of these nanoscale objects is determined not only by thermal mobility, but also by their interactions with cellular structures (e.g. cytoskeletal filaments), molecular-scale entities (e.g. motor proteins, signaling molecules), and other nanoscale entities. The complex and multi-scale nature of these interactions has made understanding and prediction of nanoscale transport phenomena tremendously difficult.

Our work aims at developing an integrated and comprehensive computational framework, SimCell (Simulation of Discrete Nanoscale Transports in Cell), to describe, analyze and predict the biophysical and biochemical processes associated with transport of discrete nanoscale entities at the local, cellular and sub-cellular, level. Such framework will enable synthesis and organization of existing information, testing hypotheses and suggesting future experiments. The basic modeling principles are (i) Realistic representation of cell geometry and cellular structures, (ii) Discrete and mechanistic description of physical and transport processes, and (iii) Spatial-temporal evolution of the whole-cell as a complex and dynamic system. The approach brings out the complexity introduced by intracellular organization, spatial compartmentalization, transport dynamics and stochastic fluctuations.

In this presentation, we will discuss the development and experimental validation of SimCell, and summarize its contributions to understanding of organelle organization and rational design of nanoscale drug and gene carriers.