Mechanical interaction of cells and ECM in 3D

March 26, 2019

Cells are constantly interacting with their surrounding extracellular matrix (ECM). They spread, contract, and migrate in these biopolymer networks. We are interested in developing tools to probe the mechanical interaction of between cells and ECM, such as contractile stresses, and cell induced mechanical properties changes of the surrounding ECM.

Optical Method Development for Cell Mechanics

Mechanical properties of cells are important for a variety of cell physiological and pathological processes. Our group has been developing optics based micromechanical measurement tools to enable mechanics of cells to be measured in 3D and in situ. We are also interested in applying these tools to characterize the mechanics of cells during disease and developmental processes.

Mechanical Fingerprinting of Cells

The cytoplasm of mammalian cells is a highly complex environment. It is extremely dynamic, yet highly crowded, and functions at far from equilibrium. The mechanical property of cell cytoplasm is vital to cell function as it provides the environment for all intracellular processes. Our group is interested in probing the complex mechanical properties of the cytoplasm in a broad spectrum of loading strain and strain rate, aiming to provide a mechanical state diagram for the cytoplasm.

Mechanics of Cancer

June 30, 2019

Sculpting of structure and function of three-dimensional multicellular tissues depend critically on the spatial and temporal coordination of cellular physical properties. Yet the organizational principles that govern these events, and their disruption in disease, remain poorly understood.  We are excited about the potential for employing the micromechanical measurement tools we developed to trace the spatiotemporal evolution of cell mechanics during the development of multicellular systems, such as a developing embryo or cancerous tumor. For example, using a multicellular mammary cancer organoid model, we map in three dimensions the spatial and temporal evolution of positions, motions, and physical characteristics of individual cells. Compared with cells in the organoid core, cells at the organoid periphery and the invasive front are found to be systematically softer, larger and more dynamic. We aim to characterize and understand the role of such spatiotemporal coordination of cellular physical properties in tissue organization and disease progression. 

Nonlinear Mechanics of Vimentin Intermediate Filaments

In many developmental and pathological processes, including cellular migration during normal development and invasion in cancer metastasis, cells are required to withstand severe deformations. The structural integrity of eukaryotic cells under small deformations has been known to depend on the cytoskeleton including actin filaments (F-actin), microtubules (MT) and intermediate filaments (IFs). However, it remains unclear how cells resist severe deformations since both F-actin and microtubules fluidize or disassemble under moderate strains. Using vimentin containing IFs (VIFs) as a model for studying the large family of IF proteins, we demonstrate that they dominate cytoplasmic mechanics and maintain cell viability at large deformations. Our results show that cytoskeletal VIFs form a stretchable, hyperelastic network in living cells. This network works synergistically with other cytoplasmic components, substantially enhancing the strength, stretchability, resilience and toughness of cells. Moreover, we find the hyperelastic VIF network, together with other quickly recoverable cytoskeletal components, form a mechanically robust structure with a self-healing nature.

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