Wound Healing: Better Understanding of How Skin Cells Close Gaps

Chwee Teck (C.T.) LIM PhD Provost’s Chair Professor, Deputy Head, Department of Biomedical Engineering & Department of Mechanical Engineering Principal Investigator, Mechanobiology Institute Faculty Fellow, Singapore-MIT Alliance for Research & Technology (SMART) National University of Singapore Faculty of Engineering, SingaporeMedicalResearch.com Interview with:
Chwee Teck (C.T.) LIM PhD
Provost’s Chair Professor, Deputy Head, Department of Biomedical Engineering & Department of Mechanical Engineering
Principal Investigator, Mechanobiology Institute
Faculty Fellow, Singapore-MIT Alliance for Research & Technology (SMART) National University of Singapore

 

Medical Research: What is the background for this study? What are the main findings?

Professor Chwee Teck Lim: Epithelial cells have a natural tendency to close gaps and this feature plays a crucial role in many biological processes such as embryological development and wound healing. For example, skin does consist of epithelial cells that when wounded, will elicit closure to initiate healing.  How epithelial cells close such gaps has always fascinated researchers from across many disciplines. It is generally accepted that two major mechanisms exist that underlie such a closure. The first is a “cell-crawling” mechanism wherein cells at the edge of the gap actively send protrusions or lamellipodia and use them as footholds to migrate over the gap. However, such a migration requires that the gap is conducive for cells to attach and form adhesions or footholds. The second mechanism is based on a coordinated contraction of multiple bundles of cellular cytoskeletal components (bundles of actin) in a manner similar to that of a “purse-string”.

Despite many studies, it has always been difficult to understand and characterize these processes separately since most often they co-exist. In this study, we show that keratinocyte monolayers have a tendency to close circular non-adhesive gaps (gaps that have been coated with a polymer that does not allow cells to adhere or form foot-holds) through contraction of bundles of actin within cells at the edge of the gap. We find that such as closure is strongly affected by the size of the gap (gaps more than 150 um in diameter have a tendency to close only partially), curvature of the gap (gaps with high curvature show better closure), and strength of intercellular adhesion (poor intercellular adhesion completely inhibits closure of non-adhesive gaps).

Medical Research: What should clinicians and patients take away from your report?

Professor Chwee Teck Lim: Wound healing is an extremely complicated process. Research in this field is directed at understanding the various mechanisms involved in this process so that more efficient methods and strategies for wound healing can be developed. Our research provides us with the fundamental understanding of how skin cells have the ability to “bridge gaps” even in the absence of a substrate that is suitable for cell adhesion. Furthermore, the critical sizes and curvature of the gaps are a good starting point for optimization of tissue engineered scaffolds for skin grafts.

Medical Research: What recommendations do you have for future research as a result of this study?

Professor Chwee Teck Lim: One of the most important findings in our studies is that some epithelial cells, e.g. renal epithelial cells, are unable to close such gaps as effectively and efficiently as keratinocytes. We believe that the answer to this lies in the organization of intercellular adhesion as well as the components of cytoskeletal components such as keratins between the two cell types. Future work will be directed towards precisely understanding the origin of these differences. This will help us to evolve better strategies for wound healing for different types of tissues with different cell types.

Citation:

Mechanics of epithelial closure over non-adherent environments

 Sri Ram Krishna Vedula,Grégoire Peyret,Ibrahim Cheddadi,Tianchi Chen,Agustí Brugués,Hiroaki Hirata,Horacio Lopez-Menendez,Yusuke Toyama,Luís Neves de Almeida,Xavier Trepat,Chwee Teck Lim & Benoit Ladoux

Nature Communications 6, Article number: 6111

doi:10.1038/ncomms7111

MedicalResearch.com Interview with: Chwee Teck (C.T.) LIM PhD (2015). Wound Healing: Skin Cells Better At Closing Gaps Than Other Organs