Cells in tissues are constantly exposed to physical forces such as hydrostatic pressure, shear stress, and compression and tension. These forces are sensed by cells through mechanoreceptors, which trigger reciprocal actomyosin- and cytoskeleton-dependent cell-generated force, a process called mechanoreciprocity. Loss of mechanoreciprocity promotes disease progression, including cancer. Mechanical properties of tissues influence disease progression, treatment effectiveness, and cancer risk. Cells dynamically adapt to forces by modifying behavior and remodelling their microenvironment, involving epigenetic changes and physical links between the matrix and nucleus. These changes affect gene expression and are altered in diseases like cancer. Mechanical forces regulate cell fate, tissue development, and postnatal function. While biochemical pathways are well understood, the role of force in regulating cell fate and tissue phenotype is less clear. Cells in tissues like the heart, lung, and skeleton experience nanoscale to macroscale forces essential for their function. These forces can be parallel or perpendicular, such as shear stress from blood flow or compressive stress from weight-bearing on bone. All cells experience isometric force through interactions with the ECM and neighboring cells, influencing cell function via actomyosin contractility and actin dynamics. Mechanical forces are crucial for normal tissue-specific development, orchestrating tissue organization and function, and regulating cell growth, survival, and migration. The lung epithelium undergoes branching morphogenesis due to progressive end bud enlargement. Force also regulates the integrity of the final lung ductal tree through cyclic shear stress from fetal breathing movements. Disrupting Rho-dependent cytoskeletal tension affects basement membrane thickness and lung epithelial duct organization. Adult tissue homeostasis requires a balance of forces. Skeletal health depends on mechanical loading, with exercise increasing proteoglycan content in cartilage. Force facilitates bone matrix deposition, and immobilization reduces bone mineral density. Vascular function is largely determined by fluid shear stress, which directs endothelial cells to align with flow direction. Each tissue has a characteristic 'stiffness phenotype', with cellular components having unique rheology and stiffness optima that change during development, function, or pathology. The physical properties of the ECM and cellular rheology significantly influence cellular behaviors such as differentiation, tissue organization, and cell migration. Mechanotransduction and mechanoreciprocity involve cells sensing and responding to mechanical cues. Integrins, which interact with the ECM and cytoskeleton, are key mechanotransducers. Force activates integrins, facilitating their maturation into focal adhesions and promoting RhoGTPase-dependent actomyosin contractility. Force-induced conformational changes in integrin-associated molecules like talin 1 reveal binding sites for vinculin and alter integrin adhesion. Force-dependent activation of signaling cascades allows cells to respond to dynamic force environments. Force-activated Erk cooperates with other kinases to induce cell proliferation or sustain survival. Compression stress affects microCells in tissues are constantly exposed to physical forces such as hydrostatic pressure, shear stress, and compression and tension. These forces are sensed by cells through mechanoreceptors, which trigger reciprocal actomyosin- and cytoskeleton-dependent cell-generated force, a process called mechanoreciprocity. Loss of mechanoreciprocity promotes disease progression, including cancer. Mechanical properties of tissues influence disease progression, treatment effectiveness, and cancer risk. Cells dynamically adapt to forces by modifying behavior and remodelling their microenvironment, involving epigenetic changes and physical links between the matrix and nucleus. These changes affect gene expression and are altered in diseases like cancer. Mechanical forces regulate cell fate, tissue development, and postnatal function. While biochemical pathways are well understood, the role of force in regulating cell fate and tissue phenotype is less clear. Cells in tissues like the heart, lung, and skeleton experience nanoscale to macroscale forces essential for their function. These forces can be parallel or perpendicular, such as shear stress from blood flow or compressive stress from weight-bearing on bone. All cells experience isometric force through interactions with the ECM and neighboring cells, influencing cell function via actomyosin contractility and actin dynamics. Mechanical forces are crucial for normal tissue-specific development, orchestrating tissue organization and function, and regulating cell growth, survival, and migration. The lung epithelium undergoes branching morphogenesis due to progressive end bud enlargement. Force also regulates the integrity of the final lung ductal tree through cyclic shear stress from fetal breathing movements. Disrupting Rho-dependent cytoskeletal tension affects basement membrane thickness and lung epithelial duct organization. Adult tissue homeostasis requires a balance of forces. Skeletal health depends on mechanical loading, with exercise increasing proteoglycan content in cartilage. Force facilitates bone matrix deposition, and immobilization reduces bone mineral density. Vascular function is largely determined by fluid shear stress, which directs endothelial cells to align with flow direction. Each tissue has a characteristic 'stiffness phenotype', with cellular components having unique rheology and stiffness optima that change during development, function, or pathology. The physical properties of the ECM and cellular rheology significantly influence cellular behaviors such as differentiation, tissue organization, and cell migration. Mechanotransduction and mechanoreciprocity involve cells sensing and responding to mechanical cues. Integrins, which interact with the ECM and cytoskeleton, are key mechanotransducers. Force activates integrins, facilitating their maturation into focal adhesions and promoting RhoGTPase-dependent actomyosin contractility. Force-induced conformational changes in integrin-associated molecules like talin 1 reveal binding sites for vinculin and alter integrin adhesion. Force-dependent activation of signaling cascades allows cells to respond to dynamic force environments. Force-activated Erk cooperates with other kinases to induce cell proliferation or sustain survival. Compression stress affects micro