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Biophysical stimuli presented to cells via microenvironmental properties (e.g., alignment and stiffness) or external forces have a significant impact on cell function and behavior. Recently, the cell nucleus has been identified as a mechanosensitive organelle that contributes to the perception and response to mechanical stimuli. However, the specific mechanotransduction mechanisms that mediate these effects have not been clearly established. Here, we offer a comprehensive review of the evidence supporting (and refuting) three hypothetical nuclear mechanotransduction mechanisms: physical reorganization of chromatin, signaling at the nuclear envelope, and altered cytoskeletal structure/tension due to nuclear remodeling. Our goal is to provide a reference detailing the progress that has been made and the areas that still require investigation regarding the role of nuclear mechanotransduction in cell biology. Additionally, we will briefly discuss the role that mathematical models of cell mechanics can play in testing these hypotheses and in elucidating how biophysical stimulation of the nucleus drives changes in cell behavior. While force-induced alterations in signaling pathways involving lamina-associated polypeptides (LAPs) (e.g., emerin and histone deacetylase 3 (HDAC3)) and transcription factors (TFs) located at the nuclear envelope currently appear to be the most clearly supported mechanism of nuclear mechanotransduction, additional work is required to examine this process in detail and to more fully test alternative mechanisms. The combination of sophisticated experimental techniques and advanced mathematical models is necessary to enhance our understanding of the role of the nucleus in the mechanotransduction processes driving numerous critical cell functions.
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http://dx.doi.org/10.1115/1.4035350 | DOI Listing |
J Biomed Mater Res A
January 2025
Department of Bioengineering, Stanford University, Stanford, California, USA.
Osteoarthritis (OA) is a prevalen degenerative joint disease with no FDA-approved therapies that can halt or reverse its progression. Current treatments address symptoms like pain and inflammation, but not underlying disease mechanisms. OA progression is marked by increased inflammation and extracellular matrix (ECM) degradation of the joint cartilage.
View Article and Find Full Text PDFNuclear deformation by osmotic shock or necrosis activates the cytosolic phospholipase A2 (cPla2) nuclear shape sensing pathway, a key regulator of tissue inflammation and repair. Ca²⁺ and inner nuclear membrane (INM) tension (T ) are believed to mediate nucleoplasmic cPla2 activation. The concept implies that T persists long enough to stimulate cPla2-INM adsorption.
View Article and Find Full Text PDFCell Prolif
December 2024
Department of Orthodontics, Faculty of Medicine, Justus Liebig University, Giessen, Germany.
Cellular mechanotransduction is a complex physiological process that integrates alterations in the external environment with cellular behaviours. In recent years, the role of the nucleus in mechanotransduction has gathered increased attention. Our research investigated the involvement of lamin A/C, a component of the nuclear envelope, in the mechanotransduction of macrophages under compressive force.
View Article and Find Full Text PDFMetabolism
December 2024
Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Department of Orthopaedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Hunan Engineering Research Center of Artificial Intelligence Based Medical Equipment, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China. Electronic address:
Skeletal muscle is a crucial tissue for physical activity and energy metabolism. Muscle atrophy, characterized by the loss of muscle mass and strength, contributes to adverse outcomes among individuals. This study elucidated the involvement of the nuclear lamina component PRR14 in transmitting mechanical signals and mediating the impact of exercise on skeletal muscle.
View Article and Find Full Text PDFMethods Mol Biol
December 2024
Raman Research Institute, Bangalore, Karnataka, India.
Biological cells sample their surrounding microenvironments using nanoscale force sensors on the cell surfaces. These surface-based force and stress sensors generate physical and chemical responses inside the cell. The inherently well-connected cytoskeleton and its physical contacts with the force elements on the nuclear membrane lead these physicochemical responses to cascade all the way inside the cell nucleus, physically altering the nuclear state.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!