Micromechanics of cellularized biopolymer networks.

Collagen gels are widely used in experiments on cell mechanics because they mimic the extracellular matrix in physiological conditions. Collagen gels are often characterized by their bulk rheology; however, variations in the collagen fiber microstructure and cell adhesion forces cause the mechanical properties to be inhomogeneous at the cellular scale. We study the mechanics of type I collagen on the scale of tens to hundreds of microns by using holographic optical tweezers to apply pN forces to microparticles embedded in the collagen fiber network. We find that in response to optical forces, particle displacements are inhomogeneous, anisotropic, and asymmetric. Gels prepared at 21 °C and 37 °C show qualitative difference in their micromechanical characteristics. We also demonstrate that contracting cells remodel the micromechanics of their surrounding extracellular matrix in a strain- and distance-dependent manner. To further understand the micromechanics of cellularized extracellular matrix, we have constructed a computational model which reproduces the main experiment findings.

Stress-induced plasticity of dynamic collagen networks.

The structure and mechanics of tissues is constantly perturbed by endogenous forces originated from cells, and at the same time regulate many important cellular functions such as migration, differentiation, and growth. Here we show that 3D collagen gels, major components of connective tissues and extracellular matrix (ECM), are significantly and irreversibly remodeled by cellular traction forces, as well as by macroscopic strains. To understand this ECM plasticity, we develop a computational model that takes into account the sliding and merging of ECM fibers. We have confirmed the model predictions with experiment. Our results suggest the profound impacts of cellular traction forces on their host ECM during development and cancer progression, and suggest indirect mechanical channels of cell-cell communications in 3D fibrous matrices.The structure and mechanics of tissues is constantly perturbed by endogenous forces originated from cells. Here the authors show that 3D collagen gels, major components of connective tissues and extracellular matrix, are significantly and irreversibly remodelled by cellular traction forces and by macroscopic strains.

Three-Dimensional Reflectance Traction Microscopy.

Cells in three-dimensional (3D) environments exhibit very different biochemical and biophysical phenotypes compared to the behavior of cells in two-dimensional (2D) environments. As an important biomechanical measurement, 2D traction force microscopy can not be directly extended into 3D cases. In order to quantitatively characterize the contraction field, we have developed 3D reflectance traction microscopy which combines confocal reflection imaging and partial volume correlation postprocessing. We have measured the deformation field of collagen gel under controlled mechanical stress. We have also characterized the deformation field generated by invasive breast cancer cells of different morphologies in 3D collagen matrix. In contrast to employ dispersed tracing particles or fluorescently-tagged matrix proteins, our methods provide a label-free, computationally effective strategy to study the cell mechanics in native 3D extracellular matrix.