Molecular Simulations of Biological Active Matter

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Professor Garegin Papoian from the University of Maryland-College Park is supported by an award from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry to advance theoretical understanding and computational modeling of active matter. The latter is fundamentally different from traditional states of matter, such as solids, liquids, and gases. In active matter systems, the individual particles consume energy, propelling them along directional motions, where the mutual interactions of these motorized particles lead to a wide variety of far-from-equilibrium phases with exotic behaviors. The cell is by far the most important example of active matter, where chemistry and mechanics are strongly coupled, for example, allowing the cell to crawl around and actively sense the extracellular environment. Prof. Papoian’s group has been developing a novel research platform, called MEDYAN, which enables computer simulations of complex active matter systems. Prof. Papoian’s laboratory will work on a new representation of cytoskeletal filaments within MEDYAN, anticipating great increase in the sophistication of modeling of various nonlinear deformations of cytoskeletal networks. His group will develop algorithms that take into account chemistry dynamics on deformable membranes, which, in turn, will enable simulations of many interesting cellular processes, such as receptor clustering and cellular signaling. Longer-term, the development of MEDYAN will pave the way for in silico modeling of the whole cell at a single molecule resolution. The PI is also continuing his various educational and outreach activities, in particular, serving as physical chemistry lecturer for the US National Chemistry Olympiad Team of high school students.Prof. Papoian’s approach is based on a novel simulation framework developed in his group, called MEDYAN (the Mechanochemical Dynamics of Active Networks). It is a highly intricate reactive force field, targeted at micrometer scale complex molecular systems, such as deformable vesicles containing a mixture of various chemical species and polymers. MEDYAN interleaves chemical dynamics with mechanical equilibration, comprehensively covering in particular many important components of the cellular cytoskeleton. Prof. Papoian’s group will rely on a sophisticated nonlinear elasticity theory to describe cytoskeletal filaments in MEDYAN, enabling, for the first-time, structure-based studies of torsional and chiral effects in large cytoskeletal networks. In particular, Prof. Papoian’s laboratory will investigate how the chirality of actin filaments at the nanometer scale may propagate to the micrometer scale, which may lead to rotational symmetry breaking. In a different project, they are developing algorithms for simulating reaction-diffusion processes on the membrane manifold, achieving a careful distinction between surface and interior chemistries. This capability enables studies of a wide variety of exciting biological phenomena, from the aggregation of curvature inducing proteins causing formation of tubular protrusions to signaling receptor clustering in immune cells. MEDYAN has been fruitfully used by many research groups to model a variety of active matter phenomena, from soft matter to cell biology. The ongoing developments will further broaden its appeal, from various new researches to high school demonstrations.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.