Focal adhesions play an important role in cell spreading,migration,and overall mechanical integrity.The relationship of cell structural and mechanical properties was investigated in the context of focal adhesion proce...Focal adhesions play an important role in cell spreading,migration,and overall mechanical integrity.The relationship of cell structural and mechanical properties was investigated in the context of focal adhesion processes.Combined atomic force microscopy(AFM) and laser scanning confocal microscopy(LSCM) was utilized to measure single cell mechanics,in correlation with cellular morphology and membrane structures at a nanometer scale.Characteristic stages of focal adhesion were verified via confocal fluorescent studies,which confirmed three representative F-actin assemblies,actin dot,filaments network,and long and aligned fibrous bundles at cytoskeleton.Force-deformation profiles of living cells were measured at the single cell level,and displayed as a function of height deformation,relative height deformation and relative volume deformation.As focal adhesion progresses,single cell compression profiles indicate that both membrane and cytoskeleton stiffen,while spreading increases especially from focal complex to focal adhesion.Correspondingly,AFM imaging reveals morphological geometries of spherical cap,spreading with polygon boundaries,and elongated or polarized spreading.Membrane features are dominated by protrusions of 41-207 nm tall,short rods with 1-6 μm in length and 10.2-80.0 nm in height,and long fibrous features of 31-246 nm tall,respectively.The protrusion is attributed to local membrane folding,and the rod and fibrous features are consistent with bilayer decorating over the F-actin assemblies.Taken collectively,the reassembly of F-actin during focal adhesion formation is most likely responsible for the changes in cellular mechanics,spreading morphology,and membrane structural features.展开更多
Intermittent fasting(IF)is a convenient dietary intervention for multiple diseases,including type 2 diabetes.However,whether it can be used as a long-term antidiabetic approach is still unknown.Here,we confirm that IF...Intermittent fasting(IF)is a convenient dietary intervention for multiple diseases,including type 2 diabetes.However,whether it can be used as a long-term antidiabetic approach is still unknown.Here,we confirm that IF alone is beneficial for both moderate and severe diabetic mice,but its antidiabetic effects clearly diminish at later stages,especially for severe diabetic db/db mice,which have obviously impaired autophagy.We found that static magnetic fields can directly promote actin assembly and boost IF-induced autophagy.Consequently,the pancreatic islet and liver were improved,and the antidiabetic effects of IF were boosted.In fact,at later stages,combined static magnetic field and IF could reduce the blood glucose level of moderate type 2 diabetic mice by 40.5%(P<0.001)and severe type 2 diabetes by 34.4%(P<0.05),when IF alone no longer has significant blood glucose reduction effects.Therefore,although IF is generally beneficial for diabetes,our data reveal its insufficiency for late-stage diabetes,which can be compensated by a simple,noninvasive,long-lasting,and nonpharmacological strategy for effective long-term diabetic control.展开更多
Rho GTPases are essential regulators of the actin cytoskeleton.They are involved in various physiological and biochemical processes such as the regulation of cytoskeleton dynamics,development,proliferation,survival,an...Rho GTPases are essential regulators of the actin cytoskeleton.They are involved in various physiological and biochemical processes such as the regulation of cytoskeleton dynamics,development,proliferation,survival,and regeneration.During the development of cochlear hair cells,Rho GTPases are activated by various extracellular signals through membrane receptors to further stimulate multiple downstream effectors.Specifically,RhoA,Cdc42,and Rac1,members of the classical subfamily of the Rho GTPase family,regulate the development and maintenance of cilia by inducing the polymerization of actin monomers and stabilizing actin filaments.In addition,they also regulate the normal morphology orientation of ciliary bundles in auditory hair cells,which is an important element of cell polarity regulation.Moreover,the actin-related pathways mediated by RhoA,Cdc42,and Rac1 also play a role in the motility of outer hair cells,indicating that the function of Rho GTPases is crucial in the highly polar auditory sensory system.In this review,we focus on the expression of RhoA,Cdc42,and Rac1 in cochlear hair cells and how these small molecules participate in ciliary bundle morphogenesis and cochlear hair cell movement.We also discuss the progress of current research investigating the use of these small molecules as drug targets for deafness treatment.展开更多
基金initiated by a UCD Alzheimer's Disease Center (ADC) pilotgranta CRCC (Cancer Research Coordination Committee) Research Grantthe support of W. M. Keck Foundation
文摘Focal adhesions play an important role in cell spreading,migration,and overall mechanical integrity.The relationship of cell structural and mechanical properties was investigated in the context of focal adhesion processes.Combined atomic force microscopy(AFM) and laser scanning confocal microscopy(LSCM) was utilized to measure single cell mechanics,in correlation with cellular morphology and membrane structures at a nanometer scale.Characteristic stages of focal adhesion were verified via confocal fluorescent studies,which confirmed three representative F-actin assemblies,actin dot,filaments network,and long and aligned fibrous bundles at cytoskeleton.Force-deformation profiles of living cells were measured at the single cell level,and displayed as a function of height deformation,relative height deformation and relative volume deformation.As focal adhesion progresses,single cell compression profiles indicate that both membrane and cytoskeleton stiffen,while spreading increases especially from focal complex to focal adhesion.Correspondingly,AFM imaging reveals morphological geometries of spherical cap,spreading with polygon boundaries,and elongated or polarized spreading.Membrane features are dominated by protrusions of 41-207 nm tall,short rods with 1-6 μm in length and 10.2-80.0 nm in height,and long fibrous features of 31-246 nm tall,respectively.The protrusion is attributed to local membrane folding,and the rod and fibrous features are consistent with bilayer decorating over the F-actin assemblies.Taken collectively,the reassembly of F-actin during focal adhesion formation is most likely responsible for the changes in cellular mechanics,spreading morphology,and membrane structural features.
基金supported by National Key R&D Program of China(2023YFB3507004)National Natural Science Foundation of China(U21A20148 and 52377228)+4 种基金International Partnership Program of Chinese Academy of Sciences(116134-KYSB20210052)Heye Health Technology Chong Ming Project(HYCMP2021010)CASHIPS Director's Fund(BJPY2021A06)Collaborative Innovation Program of Hefei Science Center,CAS(2022HSC-CIP002)CAS Project for Young Scientists in Basic Research(YSBR-097).
文摘Intermittent fasting(IF)is a convenient dietary intervention for multiple diseases,including type 2 diabetes.However,whether it can be used as a long-term antidiabetic approach is still unknown.Here,we confirm that IF alone is beneficial for both moderate and severe diabetic mice,but its antidiabetic effects clearly diminish at later stages,especially for severe diabetic db/db mice,which have obviously impaired autophagy.We found that static magnetic fields can directly promote actin assembly and boost IF-induced autophagy.Consequently,the pancreatic islet and liver were improved,and the antidiabetic effects of IF were boosted.In fact,at later stages,combined static magnetic field and IF could reduce the blood glucose level of moderate type 2 diabetic mice by 40.5%(P<0.001)and severe type 2 diabetes by 34.4%(P<0.05),when IF alone no longer has significant blood glucose reduction effects.Therefore,although IF is generally beneficial for diabetes,our data reveal its insufficiency for late-stage diabetes,which can be compensated by a simple,noninvasive,long-lasting,and nonpharmacological strategy for effective long-term diabetic control.
基金supported by the Natural Science Foundation of Jiangsu Province,No.BK20221377(to JG)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China,No.22KJB180023(to JG)。
文摘Rho GTPases are essential regulators of the actin cytoskeleton.They are involved in various physiological and biochemical processes such as the regulation of cytoskeleton dynamics,development,proliferation,survival,and regeneration.During the development of cochlear hair cells,Rho GTPases are activated by various extracellular signals through membrane receptors to further stimulate multiple downstream effectors.Specifically,RhoA,Cdc42,and Rac1,members of the classical subfamily of the Rho GTPase family,regulate the development and maintenance of cilia by inducing the polymerization of actin monomers and stabilizing actin filaments.In addition,they also regulate the normal morphology orientation of ciliary bundles in auditory hair cells,which is an important element of cell polarity regulation.Moreover,the actin-related pathways mediated by RhoA,Cdc42,and Rac1 also play a role in the motility of outer hair cells,indicating that the function of Rho GTPases is crucial in the highly polar auditory sensory system.In this review,we focus on the expression of RhoA,Cdc42,and Rac1 in cochlear hair cells and how these small molecules participate in ciliary bundle morphogenesis and cochlear hair cell movement.We also discuss the progress of current research investigating the use of these small molecules as drug targets for deafness treatment.
