TY - JOUR
T1 - Molecular Regulators of Cellular Mechanoadaptation at Cell–Material Interfaces
AU - Jo, Juhyeon
AU - Abdi Nansa, Sama
AU - Kim, Dong Hwee
N1 - Funding Information:
This research was funded by National Research Foundation of Korea, grant number 2019R1A2C2004437 and 2020R1A4A3079755. This work was supported by KU-KIST Graduate School of Converging Science and Technology Program, Korea University Future Research Grants, Korea University Grant, and National Research Foundation of Korea.
Publisher Copyright:
© Copyright © 2020 Jo, Abdi Nansa and Kim.
PY - 2020/12/8
Y1 - 2020/12/8
N2 - Diverse essential cellular behaviors are determined by extracellular physical cues that are detected by highly orchestrated subcellular interactions with the extracellular microenvironment. To maintain the reciprocity of cellular responses and mechanical properties of the extracellular matrix, cells utilize a variety of signaling pathways that transduce biophysical stimuli to biochemical reactions. Recent advances in the micromanipulation of individual cells have shown that cellular responses to distinct physical and chemical features of the material are fundamental determinants of cellular mechanosensation and mechanotransduction. In the process of outside-in signal transduction, transmembrane protein integrins facilitate the formation of focal adhesion protein clusters that are connected to the cytoskeletal architecture and anchor the cell to the substrate. The linkers of nucleoskeleton and cytoskeleton molecular complexes, collectively termed LINC, are critical signal transducers that relay biophysical signals between the extranuclear cytoplasmic region and intranuclear nucleoplasmic region. Mechanical signals that involve cytoskeletal remodeling ultimately propagate into the nuclear envelope comprising the nuclear lamina in assistance with various nuclear membrane proteins, where nuclear mechanics play a key role in the subsequent alteration of gene expression and epigenetic modification. These intracellular mechanical signaling cues adjust cellular behaviors directly associated with mechanohomeostasis. Diverse strategies to modulate cell-material interfaces, including alteration of surface rigidity, confinement of cell adhesive region, and changes in surface topology, have been proposed to identify cellular signal transduction at the cellular and subcellular levels. In this review, we will discuss how a diversity of alterations in the physical properties of materials induce distinct cellular responses such as adhesion, migration, proliferation, differentiation, and chromosomal organization. Furthermore, the pathological relevance of misregulated cellular mechanosensation and mechanotransduction in the progression of devastating human diseases, including cardiovascular diseases, cancer, and aging, will be extensively reviewed. Understanding cellular responses to various extracellular forces is expected to provide new insights into how cellular mechanoadaptation is modulated by manipulating the mechanics of extracellular matrix and the application of these materials in clinical aspects.
AB - Diverse essential cellular behaviors are determined by extracellular physical cues that are detected by highly orchestrated subcellular interactions with the extracellular microenvironment. To maintain the reciprocity of cellular responses and mechanical properties of the extracellular matrix, cells utilize a variety of signaling pathways that transduce biophysical stimuli to biochemical reactions. Recent advances in the micromanipulation of individual cells have shown that cellular responses to distinct physical and chemical features of the material are fundamental determinants of cellular mechanosensation and mechanotransduction. In the process of outside-in signal transduction, transmembrane protein integrins facilitate the formation of focal adhesion protein clusters that are connected to the cytoskeletal architecture and anchor the cell to the substrate. The linkers of nucleoskeleton and cytoskeleton molecular complexes, collectively termed LINC, are critical signal transducers that relay biophysical signals between the extranuclear cytoplasmic region and intranuclear nucleoplasmic region. Mechanical signals that involve cytoskeletal remodeling ultimately propagate into the nuclear envelope comprising the nuclear lamina in assistance with various nuclear membrane proteins, where nuclear mechanics play a key role in the subsequent alteration of gene expression and epigenetic modification. These intracellular mechanical signaling cues adjust cellular behaviors directly associated with mechanohomeostasis. Diverse strategies to modulate cell-material interfaces, including alteration of surface rigidity, confinement of cell adhesive region, and changes in surface topology, have been proposed to identify cellular signal transduction at the cellular and subcellular levels. In this review, we will discuss how a diversity of alterations in the physical properties of materials induce distinct cellular responses such as adhesion, migration, proliferation, differentiation, and chromosomal organization. Furthermore, the pathological relevance of misregulated cellular mechanosensation and mechanotransduction in the progression of devastating human diseases, including cardiovascular diseases, cancer, and aging, will be extensively reviewed. Understanding cellular responses to various extracellular forces is expected to provide new insights into how cellular mechanoadaptation is modulated by manipulating the mechanics of extracellular matrix and the application of these materials in clinical aspects.
KW - cell-materials interaction
KW - cellular mechanobiology
KW - disease associated mechanoresponses
KW - mechanoadaptation
KW - mechanotransduction
UR - http://www.scopus.com/inward/record.url?scp=85098052226&partnerID=8YFLogxK
U2 - 10.3389/fbioe.2020.608569
DO - 10.3389/fbioe.2020.608569
M3 - Review article
AN - SCOPUS:85098052226
VL - 8
JO - Frontiers in Bioengineering and Biotechnology
JF - Frontiers in Bioengineering and Biotechnology
SN - 2296-4185
M1 - 608569
ER -