Martinez, D. M. | bioRxiv Science

bioRxiv2022

Thermal modulation of skin friction at the fingertip

Preliminary human studies show that reduced skin temperature minimises the risk of mechanically-induced skin damage. However, the mechanisms by which cooling enhances skin tolerance to pressure and shear remain poorly understood. We hypothesized that skin cooling below thermo-neutral conditions will decrease friction at the skin-material interface. To test our hypothesis, we measured the friction coefficient of a thermally pre-conditioned index finger sliding at a normal load (5N) across a plate maintained at three different temperatures (38, 24, and 16{square}). To quantify the temperature distribution of the skin tissue, we used 3D surface scanning and Optical Coherence Tomography to develop an anatomically-representative thermal model of the finger. Our data indicated that the sliding finger with thermally affected tissues (up to 8mm depth) experienced significantly (p<0.01) lower frictional forces at 16{degrees}C-plate temperature than at the 24{degrees}C [-23% ({+/-}19% SD)] and 38{degrees}C plate interactions [-35% ({+/-}11% SD)], respectively. This phenomenon occurred without changes in skin hydration during sliding. Accordingly, our experiments demonstrate thermal modulation of skin friction in the absence of skin-moisture effects. Our complementary experimental and theoretical results provide new insight into thermal modulation of skin friction that can be employed for developing thermal technologies to maintain skin integrity under mechanical loading.

biophysics↗

bioRxiv2021

Glucocorticoid receptor collaborates with pioneer factors and AP-1 to execute genome-wide regulation

AO_SCPLOWBSTRACTC_SCPLOWThe glucocorticoid receptor (GR) regulates transcription through binding to specific DNA motifs, particularly at enhancers. While the motif to which it binds is constant across cell types, GR has cell type-specific binding at genomic loci, resulting in regulation of different genes. The presence of other bound transcription factors (TFs) is hypothesized to strongly influence where GR binds. Here, we addressed the roles of other TFs in the glucocorticoid response by comparing changes in GR binding and nascent transcription at promoters and distal candidate cis-regulatory elements (CCREs) in two distinct human cancer cell types. We found that after glucocorticoid treatment, GR binds to thousands of genomic loci that are primarily outside of promoter regions and are potentially enhancers. The majority of these GR binding sites are cell-type specific, and they are associated with pioneer factor binding. A small fraction of GR occupied regions (GORs) displayed increased bidirectional nascent transcription, which is a characteristic of many active enhancers, after glucocorticoid treatment. Non-promoter GORs with increased transcription were specifically enriched for AP-1 binding prior to glucocorticoid treatment. These results support a model of transcriptional regulation in which multiple classes of TFs are required. The pioneer factors increase chromatin accessibility, facilitating the binding of GR and additional factors. AP-1 binding poises a fraction of accessible sites to be rapidly transcribed upon glucocorticoid-induced GR binding. The coordinated activity of multiple TFs then results in cell type-specific changes in gene expression. We anticipate that many models of inducible gene expression also require multiple distinct TFs that act at multiple steps of transcriptional regulation.

genomics↗