title: Substrate elasticity as biomechanical modulator of tissue homeostatic parameters in corneal keratinocytes.
abstract: This study aimed at identifying putative modulations of tissue homeostatic parameters in corneal keratinocytes in response to biomechanical cues as basis for innovative cornea biomechanical-tailored biomaterials. Since cornea epithelial biomechanics is already described for contacts on nanostructures, we herein analyzed cell response to mechanical substrate elasticity. Therefore, corneal keratinocytes were established on physiologically-relevant elastic substrates of 40kPa, 130kPa but also on non-physiological stiff substrates of 1.74MPa for 3 days. qPCR revealed that changes in gene expression were only marginal between 40kPa and 130kPa, while significant modulations were seen on 1.74MPa substrates for most tissue-innate biomarkers under study. Gene expression fairly coincided with the protein, with differentiation progression biomarkers involucrin and fillagrin being already significantly increased between elasticities of 40kPa and 130kPa. Regarding focal adhesions, reinforcement was seen for ß1 integrin and phospho- p(125FAK) between 40kPa and 130kPa, while from 130kPa to 1.74MPa actin redistributed and phospho-p(125FAK) was strikingly up-regulated. These findings suggest elasticity dependence for differentiation progression and focal adhesion dynamics of corneal keratinocytes, supporting the concept of biomechanics governed regulation of tissue homeostasis. Moreover, this concept in turn can be translated into prospective cornea-tailored biomaterials for therapeutic approaches in ophthalmology.
authors.affiliation: Department of Oral Biotechnology, Dental School, University Medical Center Freiburg, Hugstetterstrasse 55, 79106 Freiburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Moers
authors.affiliation: Department of Oral Biotechnology, Dental School, University Medical Center Freiburg, Hugstetterstrasse 55, 79106 Freiburg, Germany. Electronic address: thorsten.steinberg@uniklinik-freiburg.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Steinberg
authors.affiliation: University Eye Hospital, University Hospital Freiburg, Kilianstrasse 5, 79106 Freiburg, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Schlunck
authors.affiliation: University Eye Hospital, University Hospital Freiburg, Kilianstrasse 5, 79106 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinhard
authors.affiliation: Department of Oral Biotechnology, Dental School, University Medical Center Freiburg, Hugstetterstrasse 55, 79106 Freiburg, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Tomakidi
authors.affiliation: University Eye Hospital, University Hospital Freiburg, Kilianstrasse 5, 79106 Freiburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Eberwein
mesh_terms: D001672:Biocompatible Materials; D001696:Biomechanical Phenomena; D003315:Cornea / Q000166:cytology* / Q000378:metabolism; D004548:Elasticity; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D001672:Biocompatible Materials; D019012:Integrin beta1; D051416:Focal Adhesion Protein-Tyrosine Kinases