Brown University

Three-Dimensional Kinematic Measurements of Nonlinear Deformations in Cellular Biology

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Abstract:
The mechanical interaction between cells and their microenvironments is a significant factor affecting biological and physiological processes. Cell-matrix interactions have historically been measured by computing cell-induced forces using a well-established technique, traction force microscopy (TFM). TFM assumes that the surrounding microenvironment has well characterized linear elastic mechanical properties, only applicable for small deformations. However, the linear elastic assumption is invalid for many synthetic and native tissues since the underlying microstructure is heterogeneous and exhibits a nonlinear deformation response to loading. Presented here are new experimental analysis techniques that measure the kinematic signatures of nonlinear deformations without relying on the material properties of the matrix. An algorithm called fast iterative digital volume correlation (FIDVC) is developed to noninvasively track the nonlinear motion of materials from three-dimensional (3D) images within pragmatic computation times. FIDVC is applied to measure the nonlinear surface deformations generated by neutrophils migrating through a fibrillar material that is not mechanically characterized. Visualization techniques are presented that make it easier to interpret the spatially complex 3D patterns of the deformation field. A new mathematical framework is developed to convert these complex surface measurements to simple yet powerful metrics that provide information about the overall expansion/contraction and rotational behavior of the cell. These metrics may be used by researchers to investigate the cellular migration mechanisms in more complex, physiologically relevant materials. Another application of kinematic analysis is presented to study the cellular injury response to externally applied deformations. An electromechanical device is built to apply uniaxial compression to neurons embedded in a heterogeneous microenvironment. New kinematic analysis techniques are developed to show that neuron death is correlated with the orientation-dependent mean strain experienced by the cell during deformation.
Notes:
Thesis (Ph.D. -- Brown University (2015)

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Citation

Bar-Kochba, Eyal, "Three-Dimensional Kinematic Measurements of Nonlinear Deformations in Cellular Biology" (2015). Mechanics of Solids Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.7301/Z05X279M

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