(41g) Can Soft Signals Turn Oncogenic? a Soft-Matter and Multiscale Modeling Approach to Engineering Cancer Cells and Inform Therapies (Invited Speaker)

The talk will focus on building predictive models in cell biology and bioengineering using equilibrium and non-equilibrium statistical mechanics, and collaboratively validating such models in in vitro physical science-based experiments, in vivo in cell culture, and in vivo in model organisms and human trials.

A theme, we discuss in relation to tumors of the soft tissues, the question “Can Soft Signals Turn Oncogenic?” There are emerging links between the stiffness of the tissue microenvironment and the tumorogenicity in several tumors of soft tissues, thereby bringing to light the importance of how cells transduce mechanical signals to alter signals and cell fate. We focus on molecular and subcellular mechanisms of curvature induction and sensing in cell membranes by a novel class of membrane remodeling proteins. We demonstrate how membrane morphologies such as protrusions can serve as signaling hubs to initiate and sustain survival as well as proliferative pathways in single cells that are initiated solely by physical stimulus and without any external biochemical cues.

We show that mechanism for cell-cell interactions and signaling communications can be potently mediated by extracellular vesicles (exosomes and macrovesicles) whose biogenesis is controlled by the mechanobiology of the cell and the extracellular microenvironment. Exosome-mediated intercellular signaling can potentiate immune response in cancer and also viral infections (such as SARS-COV2 infection) and we will describe our efforts to integrate our biophysics-based approach to next generation pharmacokinetic modeling approach towards developing predictive digital twins models for optimizing therapies in cancer and beyond.

These works are funded by US NIH, NSF, and EU ERC.