Mechanical cues, such as extracellular matrix (ECM) stiffness or force, have been implicated as playing a key role in mediating breast cancer progression. We aim to understand how mechanical cues are sensed by the mammary epithelium, and what long-term alterations in gene expression these mechanical cues control. Further, the processes of cell division and cell migration, which drive tumor growth, invasion, and metastasis, are by nature physical processes involving the generation of force by cells on ECM. We are using engineered materials for 3D culture and atomic force microscopy to elucidate how cells generate forces to drive cell division and migration during tumor growth and metastasis. Our vision is that by better understanding the role of mechanics in breast cancer, we can develop more effective diagnostics and therapies.
Selected publications: Chaudhuri, et al., Extracellular matrix stiffness and composition jointly regulate the induction of malignant phenotypes in mammary epithelium, Nature Materials (2014); Lee and Chaudhuri, Regulation of breast cancer progression by extracellular matrix mechanics: insights from 3D culture models, ACS Biomat. Sci. and Eng. (2017).
Mechanotransduction refers to the process by which cells sense and respond to mechanical cues. It has been found that cells sense and respond to extracellular matrix (ECM) elasticity. However, reconstituted ECM and living tissues are typically viscoelastic and exhibit stress relaxation. We have found that various cellular behaviors, such as spreading, proliferation, and differentiation, are regulated independently by both the elastic and viscous, or time dependent, properties of extracellular matrix materials. We seek to elucidate the viscoelastic properties of physiologically relevant extracellular matrices, identify other biological processes that are sensitive to viscoelasticity and the mechanisms by which viscoelasticity influences these processes, and ultimately utilize this property as a design parameter for biomaterials in regenerative medicine.
Selected publications: Chaudhuri, et al., Hydrogels with tunable stress relaxation regulate stem cell fate and activity, Nature Materials (2015); Nam, et al., Strain-enhanced stress relaxation impacts nonlinear elasticity in collagen gels, PNAS (2016); Nam, et al., Viscoplasticity Enables Mechanical Remodeling of Matrix by Cells, Biophysical Journal (2016). Lee, et al, Mechanical confinement regulates cartilage matrix formation by chondrocytes, Nature Materials (2017).
Many biological materials, from the actin cytoskeleton inside cells, which governs their shape and rigidity, to the extracellular matrix, consist of semiflexible biopolymer networks. These networks are typically organized in specific architectures, and are often under tensional or compressional forces. These networks often have unique behaviors of nonlinear elasticity, viscoelasticity, and toughness but the molecular mechanisms underlying these behaviors are not fully understood. Our goal is to elucidate the molecular mechanisms that govern the mechanics of these networks, and to use this understanding to engineer biomaterials with useful mechanical properties for use in tissue engineering and other applications.
Selected publications: Lam, Chaudhuri, et al., Mechanics and contraction dynamics of single platelets and implications for clot stiffening, Nature Materials (2011); Chaudhuri, et al., Reversible stress softening of actin networks, Nature (2007); Nam, et al., Strain-enhanced stress relaxation impacts nonlinear elasticity in collagen gels, PNAS (2016).