Mechanics of the cell: Interaction mechanisms and mechanobiological models.

The importance of cell mechanics has long been recognized for the cell development and function. Biomechanics plays an important role in cell metabolism, regulation of mechanotransduction pathways and also modulation of nuclear response. The mechanical properties of the cell are likely determined by, among many others, the cytoskeleton elasticity, membrane tension and cell-substrate adhesion. This coordinated but complex mechanical interplay is required however, for the cell to respond to and influence in a reciprocal manner the chemical and mechanical signals from the extracellular matrix (ECM). In an effort to better and more fully understand the cell mechanics, the role of nuclear mechanics has emerged as an important contributor to the overall cellular mechanics. It is not too difficult to appreciate the physical connection between the nucleus and the cytoskeleton network that may be connected to the ECM through the cell membrane. Transmission of forces from ECM through this connection is essential for a wide range of cellular behaviors and functions such as cytoskeletal reorganization, nuclear movement, cell migration and differentiation. Unlike the cellular mechanics that can be measured using a number of biophysical techniques that were developed in the past few decades, it still remains a daunting challenge to probe the nuclear mechanics directly. In this paper, we therefore aim to provide informative description of the cell membrane and cytoskeleton mechanics, followed by unique computational modeling efforts to elucidate the nucleus-cytoskeleton coupling. Advances in our knowledge of complete cellular biomechanics and mechanotransduction may lead to clinical relevance and applications in mechano-diseases such as atherosclerosis, stem cell-based therapies, and the development of tissue engineered products.

Correlation between Nuclear Morphology and Adipogenic Differentiation: Application of a Combined Experimental and Computational Modeling Approach.

Stem cells undergo drastic morphological alterations during differentiation. While extensive studies have been performed to examine the cytoskeletal remodeling, there is a growing interest to determine the morphological, structural and functional changes of the nucleus. The current study is therefore aimed at quantifying the extent of remodeling of the nuclear morphology of human mesenchymal stem cells during biochemically-induced adipogenic differentiation. Results show the size of nuclei decreased exponentially over time as the lipid accumulation is up-regulated. Increases in the lipid accumulation appear to lag the nuclear reorganization, suggesting the nuclear deformation is a prerequisite to adipocyte maturation. Furthermore, the lamin A/C expression was increased and redistributed to the nuclear periphery along with a subsequent increase in the nuclear aspect ratio. To further assess the role of the nucleus, a nuclear morphology with a high aspect ratio was achieved using microcontact-printed substrate. The cells with an elongated nuclear shape did not efficiently undergo adipogenesis, suggesting the cellular and nuclear processes associated with stem cell differentiation at the early stage of adipogenesis cause a change in the nuclear morphology and cannot be abrogated by the morphological cues. In addition, a novel computational biomechanical model was generated to simulate the nuclear shape change during differentiation and predict the forces acting upon the nucleus. This effort led to the development of computational scaling approach to simulate the experimentally observed adipogenic differentiation processes over 15 days in less than 1.5 hours.