| Autor: |
Hunter-Featherstone E; Department of Biosciences, Durham University, Durham DH1 3LE, UK., Young N; Department of Biosciences, Durham University, Durham DH1 3LE, UK., Chamberlain K; Department of Biosciences, Durham University, Durham DH1 3LE, UK., Cubillas P; Department of Earth Sciences, Durham University, Durham DH1 3LE, UK., Hulette B; The Procter & Gamble Company, Cincinnati, OH 45202, USA., Wei X; The Procter & Gamble Company, Cincinnati, OH 45202, USA., Tiesman JP; The Procter & Gamble Company, Cincinnati, OH 45202, USA., Bascom CC; The Procter & Gamble Company, Cincinnati, OH 45202, USA., Benham AM; Department of Biosciences, Durham University, Durham DH1 3LE, UK., Goldberg MW; Department of Biosciences, Durham University, Durham DH1 3LE, UK., Saretzki G; Biosciences Institute, Newcastle University, Newcastle-upon-Tyne NE1 7RU, UK., Karakesisoglou I; Department of Biosciences, Durham University, Durham DH1 3LE, UK. |
| Abstrakt: |
Mechanotransduction is defined as the ability of cells to sense mechanical stimuli from their surroundings and translate them into biochemical signals. Epidermal keratinocytes respond to mechanical cues by altering their proliferation, migration, and differentiation. In vitro cell culture, however, utilises tissue culture plastic, which is significantly stiffer than the in vivo environment. Current epidermal models fail to consider the effects of culturing keratinocytes on plastic prior to setting up three-dimensional cultures, so the impact of this non-physiological exposure on epidermal assembly is largely overlooked. In this study, primary keratinocytes cultured on plastic were compared with those grown on 4, 8, and 50 kPa stiff biomimetic hydrogels that have similar mechanical properties to skin. Our data show that keratinocytes cultured on biomimetic hydrogels exhibited major changes in cellular architecture, cell density, nuclear biomechanics, and mechanoprotein expression, such as specific Linker of Nucleoskeleton and Cytoskeleton (LINC) complex constituents. Mechanical conditioning of keratinocytes on 50 kPa biomimetic hydrogels improved the thickness and organisation of 3D epidermal models. In summary, the current study demonstrates that the effects of extracellular mechanics on keratinocyte cell biology are significant and therefore should be harnessed in skin research to ensure the successful production of physiologically relevant skin models. |
