Our research is focused on multiscale mechanobiology, including 1) molecular components regulating cytoskeletal networks, 2) single cells invading in complex microenvironments, and 3) multicellular systems undergoing morphogenesis and tissue-level remodeling.  Below are some of the key themes of our work. See publications for more details.



Subcellular-Scale: Dynamics of Active Cytoskeletal Networks

How do structure and functionality emerge from random mixtures of molecular constituents?  The cytoskeleton – a network of components featuring actin filaments, crosslinking proteins, and molecular motors – enables cells to acquire physical capabilities and tissues to undergo large-scaled morphological changes.  Through computational modeling, we determine how kinetics and mechanics at the molecular level modulate global mechanical properties at the network, cell, and tissue scales.  We integrate simulations and live cell experiments with fluorescently labeled cytoskeletal proteins to test our computational predictions.

 

Clustering of the cytoskeleton in live cells due to actin turnover dynamics.



Cell-Scale: Heterogeneity, Deformability, and Cell-Environment Interaction

How do cells invade across physiological, mechanical barriers during cancer metastasis?  We develop high-throughput, single-cell microfluidic techniques to investigate the invasive capabilities of individual cancer cells and to distinguish distinct phenotypes within heterogeneous tumor populations that drive cancer metastasis.  In parallel we investigate cell rheology and cell-ECM interactions in complex 3D microenvironments.

cell_gel

Cancer cells interacting inside a 3D fibrillar matrix (left) and invading across mechanical barriers (right).



Multicellular-Scale: Collective Behavior in Tumors and Tissues

How do multicellular systems self-organize and interact with the ECM in cancer and development?  We integrate experimental and computational approaches to capture the collective dynamics and mechanics of tumor spheroids, organoids, and heterotypic systems.

Collective cellular systems: invasive tumor (left), branching mammary tissue (center), and microvascular network (right) inside 3D ECM.



Biophysical Informatics

How can we better understand complex physical behaviors of cells and tissues? Biophysical informatics enables quantitative signatures to be extracted to characterize physiological and pathological biophysical phenotypes.



Biofabrication

How can we develop ultra-realistic tissues and organs? Advanced biofabrication and bioprinting utilizing fully physiological materials enable enhanced biomimicry and bioactivity in engineered tissues.

Biofabricated vascularized organoid model.