Multi-scale modeling reveals use of hierarchical tensegrity principles at the molecular, multi-molecular, and cellular levels

Mechanobiology - the discipline that focuses on the key role that mechanical forces contribute to control of biological structure and function across all size scales - requires application of multi-disciplinary approaches. These approaches span multiple fields including materials science, physics, chemistry, biology, engineering, medicine and computational modeling. Mechanobiology has been significantly advanced by the cellular tensegrity theory. This theory proposes that living systems use principles of tensegrity architecture to govern how molecules self-assemble to create multi-molecular structures, organelles, cells, tissues, organs and living organisms. Use of tensegrity provides a mechanism to control shape stability while maintaining tight integration between structure and function. It also enables mechanical information transfer from the macro-scale to the nanoscale, where mechano-chemical transduction can occur at the molecular level. While various experiments have provided data in support of the use of tensegrity by biological systems, it has not been possible to visualize how these architectural principles are utilized to build hierarchical structures of various sizes and complexity that undergo dynamic changes in form and mechanics within living cells. We recently described a new advance in multi-scale molecular simulation that combined molecular dynamic simulation methods with physics-based animation approaches, which showed how mechanical forces and deformations generated at the molecular level propagate across size scales to drive directional movement of whole cells, using sperm motility as an example (Reilly and Ingber, ACS Nano 2017, 11:12156-12166). These computer simulations also confirmed that tensegrity principles are indeed utilized at the level of individual molecules, multi-molecular assemblages, and whole living cells. Here, we explore these previous findings in greater detail in relation to tensegrity, and also describe how this simulation strategy can be used to model coupling of enzyme substrate concentrations to multiscale tensegrity-based force transduction, using mitochondrial ATP synthase as an example.