Cells respond to mechanical forces by activating specific genes and signaling pathways that allow the cells to adapt to their physical environment. Examples include muscle growth in response to exercise, bone remodeling based on their mechanical load, or endothelial cells aligning under fluid shear stress. While the involved downstream signaling pathways and mechanoresponsive genes are generally well characterized, many of the molecular mechanisms of the initiating ‘mechanosensing’ remain still elusive. In this review, we discuss recent findings and accumulating evidence suggesting that the cell nucleus plays a crucial role in cellular mechanotransduction, including processing incoming mechanoresponsive signals and even directly responding to mechanical forces. Consequently, mutations in the involved proteins or changes in nuclear envelope composition can directly impact mechanotransduction signaling and contribute to the development and progression of a variety of human diseases, including muscular dystrophy, cancer, and the focus of this review, dilated cardiomyopathy. Improved insights into the molecular mechanisms underlying nuclear mechanotransduction, brought in part by the emergence of new technologies to study intracellular mechanics at high spatial and temporal resolution, will not only result in a better understanding of cellular mechanosensing in normal cells but may also lead to the development of novel therapies in the many diseases linked to defects in nuclear envelope proteins.

Background and Purpose. Physical activity and exercise play a critical role in the management of arthritis. Understanding the factors affecting physical activity and exercise behavior is a necessary first step toward identifying the needs of, and intervention strategies for, people with arthritis. The purpose of this study was to identify factors affecting physical activity and exercise behavior in urban subjects with osteoarthritis (OA) and rheumatoid arthritis (RA). Subjects. Seventy-two consecutive subjects were recruited from the rheumatology clinic at a large urban public hospital. The sample was predominantly African American (92%), female (87%), and not working (90%). The subjects' average age was 60.9 years (SDϭ13.9, rangeϭ30 -90). Methods. Time per day spent sitting or lying down and time per week spent in exercise, leisure, and household activities were determined by individual interview. Self-efficacy, outcome expectations, disability, pain, body mass index, and social support were measured as possible explanatory factors. Results. The average daily total activity time was 3.1 hours. Household and leisure activities accounted for 85% of that time. Explanatory factors for physical activity behavior were not the same for subjects with OA and RA, despite similar between-group characteristics. Self-efficacy was present in all of the significant explanatory models. Discussion and Conclusion. The results indicate that factors that affect physical activity behavior among urban and predominantly African-American adults are dependent upon the type of physical activity and are different for people with OA and RA. Self-efficacy was the most consistent explanatory factor. [Greene BL, Haldeman GF, Kaminski A, et al. Factors affecting physical activity behavior in urban adults with arthritis who are predominantly African-American and female. Phys Ther. 2006;86:510 -519.]

Cells respond to mechanical stimulation by activation of specific signaling pathways and genes that allow the cell to adapt to its dynamic physical environment. How cells sense the various mechanical inputs and translate them into biochemical signals remains an area of active investigation. Recent reports suggest that the cell nucleus may be directly implicated in this cellular mechanotransduction process. In this chapter, we discuss how forces applied to the cell surface and cytoplasm induce changes in nuclear structure and organization, which could directly affect gene expression, while also highlighting the complex interplay between nuclear structural proteins and transcriptional regulators that may further modulate mechanotransduction signaling. Taken together, these findings paint a picture of the nucleus as a central hub in cellular mechanotransduction—both structurally and biochemically—with important implications in physiology and disease.

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