{"title":"The Driving Force: Nuclear Mechanotransduction in Cellular Function, Fate, and Disease.","authors":"Melanie Maurer, Jan Lammerding","doi":"10.1146/annurev-bioeng-060418-052139","DOIUrl":null,"url":null,"abstract":"<p><p>Cellular behavior is continuously affected by microenvironmental forces through the process of mechanotransduction, in which mechanical stimuli are rapidly converted to biochemical responses. Mounting evidence suggests that the nucleus itself is a mechanoresponsive element, reacting to cytoskeletal forces and mediating downstream biochemical responses. The nucleus responds through a host of mechanisms, including partial unfolding, conformational changes, and phosphorylation of nuclear envelope proteins; modulation of nuclear import/export; and altered chromatin organization, resulting in transcriptional changes. It is unclear which of these events present direct mechanotransduction processes and which are downstream of other mechanotransduction pathways. We critically review and discuss the current evidence for nuclear mechanotransduction, particularly in the context of stem cell fate, a largely unexplored topic, and in disease, where an improved understanding of nuclear mechanotransduction is beginning to open new treatment avenues. Finally, we discuss innovative technological developments that will allow outstanding questions in the rapidly growing field of nuclear mechanotransduction to be answered.</p>","PeriodicalId":50757,"journal":{"name":"Annual Review of Biomedical Engineering","volume":"21 ","pages":"443-468"},"PeriodicalIF":12.8000,"publicationDate":"2019-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815102/pdf/nihms-1053593.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual Review of Biomedical Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1146/annurev-bioeng-060418-052139","RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2019/3/27 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Cellular behavior is continuously affected by microenvironmental forces through the process of mechanotransduction, in which mechanical stimuli are rapidly converted to biochemical responses. Mounting evidence suggests that the nucleus itself is a mechanoresponsive element, reacting to cytoskeletal forces and mediating downstream biochemical responses. The nucleus responds through a host of mechanisms, including partial unfolding, conformational changes, and phosphorylation of nuclear envelope proteins; modulation of nuclear import/export; and altered chromatin organization, resulting in transcriptional changes. It is unclear which of these events present direct mechanotransduction processes and which are downstream of other mechanotransduction pathways. We critically review and discuss the current evidence for nuclear mechanotransduction, particularly in the context of stem cell fate, a largely unexplored topic, and in disease, where an improved understanding of nuclear mechanotransduction is beginning to open new treatment avenues. Finally, we discuss innovative technological developments that will allow outstanding questions in the rapidly growing field of nuclear mechanotransduction to be answered.
期刊介绍:
Since 1999, the Annual Review of Biomedical Engineering has been capturing major advancements in the expansive realm of biomedical engineering. Encompassing biomechanics, biomaterials, computational genomics and proteomics, tissue engineering, biomonitoring, healthcare engineering, drug delivery, bioelectrical engineering, biochemical engineering, and biomedical imaging, the journal remains a vital resource. The current volume has transitioned from gated to open access through Annual Reviews' Subscribe to Open program, with all articles published under a CC BY license.