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.

Contact and impact in the multibody dynamics of motor protein locomotion.

This paper presents the development of a rigid multibody dynamics approach to modeling, simulation, and analysis of motor proteins. A key element of this new model is that it retains the mass properties, in contrast to many commonly used models that do not. The mass properties are usually omitted because their inclusion yields a model with multiple time scales whose simulation requires a significant amount of time. However, the proposed model can be numerically integrated in a reasonable amount of time. Thus this approach represents a new method for treating multiple scale models. In addition, retaining the mass properties allows a detailed study of contact and impact between the protein and substrate, which is critical for protein processivity. The new model also provides insights into the characteristics of the protein and its environment, specifically, the effective damping experienced by the protein moving through its fluid environment may be quite small yielding under or critically damped motion. This conclusion runs contrary to the widely accepted notion that the protein's motion is strictly over damped. Herein, the differences between the motion predicted by the old and new modeling approaches are compared using a simplified model of Myosin V.

The small mass assumption applied to the multibody dynamics of motor proteins.

This paper presents a multibody dynamics approach to the modeling, simulation and analysis of motor protein dynamic behavior. Usually proteins are modeled as a collection of a small number of particles, oftentimes only two particles, with spring-like connections between them. However, these simple particle models potentially omit interactions and dynamics between the unmodeled particles and the environment that may be important. Multibody dynamics models can be used to address this issue. However, widely used techniques for analyzing particle models may not be applicable to multibody models. Herein the validity of the small mass assumption, which is central to the analysis of particle models, is examined in detail using a simplified multibody model of the molecular motor protein Myosin V.