title: Mechanical coupling of cytoskeletal elasticity and force generation is crucial for understanding the migrating nature of keloid fibroblasts.
abstract: One of the key features of keloid is its fibroblasts migrating beyond the original wound border. During migration, cells not only undergo molecular changes but also mechanical modulation. This process is led by actin filaments serving as the backbone of intra-cellular force and transduces external mechanical signal via focal adhesion complex into the cell. Here, we focus on determining the mechanical changes of actin filaments and the spatial distribution of forces in response to changing chemical stimulations and during cell migration. Atomic force microscopy and micropost array detector are used to determine and compare the magnitude and distribution of filament elasticity and force generation in fibroblasts and keloid fibroblasts. We found both filament elasticity and force generation show spatial distribution in a polarized and migrating cell. Such spatial distribution is disrupted when mechano-signalling is perturbed by focal adhesion kinase inhibitor and in keloid fibroblasts. The demonstration of keloid pathology at the nanoscale highlights the coupling of cytoskeletal function with physical characters at the subcellular level and provides new research directions for migration-related disease such as keloid.
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Hans I-Chen
authors: HI
authors: Harn
authors: Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei, Taiwan.
authors: Yang-Kao
authors: YK
authors: Wang
authors: Department of Dermatology, National Cheng Kung University Medical Hospital, Tainan, Taiwan.
authors: Chao-Kai
authors: CK
authors: Hsu
authors: Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Yen-Ting
authors: YT
authors: Ho
authors: Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Yi-Wei
authors: YW
authors: Huang
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Biomedical Engineering, College of Engineering, National Cheng Kung University, Tainan, Taiwan.
authors: Wen-Tai
authors: WT
authors: Chiu
authors: Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Hsi-Hui
authors: HH
authors: Lin
authors: Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hsinchu, Taiwan.
authors: Chao-Min
authors: CM
authors: Cheng
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors: Ming-Jer
authors: MJ
authors: Tang
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D003599:Cytoskeleton / Q000502:physiology*; D004548:Elasticity; D005347:Fibroblasts / Q000502:physiology* / Q000648:ultrastructure; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D022001:Focal Adhesions / Q000502:physiology; D006801:Humans; D007627:Keloid / Q000473:pathology*; D051379:Mice; D018625:Microscopy, Atomic Force; D041681:NIH 3T3 Cells; D015363:Quinolones / Q000494:pharmacology; D013314:Stress, Mechanical; D013450:Sulfones / Q000494:pharmacology; D014945:Wound Healing
chemical_list: C521108:6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one; D015363:Quinolones; D013450:Sulfones; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: actin; atomic force microscopy; force; keloid; migration