Controlled external chemomechanical stimuli have been shown to influence cellular and tissue regeneration/degeneration, especially with regards to distinct disease sequelae or health maintenance. Recently, a unique three-dimensional stress state was mathematically derived to describe the experimental stresses applied to isolated living cells suspended in an optohydrodynamic trap (optical tweezers combined with microfluidics). These formulae were previously developed in two and three dimensions from the fundamental equations describing creeping flows past a suspended sphere. The objective of the current study is to determine the full-field cellular strain response due to the applied three-dimensional stress environment through a multiphysics computational simulation. In this investigation, the multiscale cytoskeletal structures are modeled as homogeneous, isotropic, and linearly elastic. The resulting computational biophysics can be directly compared with experimental strain measurements, other modeling interpretations of cellular mechanics including the liquid drop theory, and biokinetic models of biomolecule dynamics. The described multiphysics computational framework will facilitate more realistic cytoskeletal model interpretations, whose intracellular structures can be distinctly defined, including the cellular membrane substructures, nucleus, and organelles. 1. Introduction The current research on human diseases primarily focuses on the molecular, microbiological, immunological, and pathological influences. The mechanical basis of disease is now often being explored to decipher any direct contributions toward the physiological response [1, 2]. In functionally loaded tissues such as cartilage and bone, cells (chondrocytes and osteocytes) experience multiaxial forces (hydrostatic, compressive, tensile, and shear), which play a significant role in modulating the biological function through maintenance of the phenotype and production of a neotissue [3]. Conversely, abnormal mechanical forces (either static or dynamic) can lead to altered cell behavior resulting in pathological matrix synthesis, increased catabolic activity (degradation), and ultimately osteoarthritis or osteoporosis (apoptosis) [4]. Our previous investigations have indicated that chondrocytes and likely other cell types respond to their stress-strain environments in a temporal and spatial manner [5]. It has also just been shown that individual cellular mechanical properties may indicate the regenerative potential of mesenchymal stem cells [6]. Investigations of the biomechanics at the
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