Hierarchy of cellular decisions in collective behavior: Implications for wound healing.

Scientific Reports
Lisa E WickertPamela K Kreeger

Abstract

Collective processes such as wound re-epithelialization result from the integration of individual cellular decisions. To determine which individual cell behaviors represent the most promising targets to engineer re-epithelialization, we examined collective and individual responses of HaCaT keratinocytes seeded upon polyacrylamide gels of three stiffnesses (1, 30, and 100 kPa) and treated with a range of epidermal growth factor (EGF) doses. Wound closure was found to increase with substrate stiffness, but was responsive to EGF treatment only above a stiffness threshold. Individual cell behaviors were used to create a partial least squares regression model to predict the hierarchy of factors driving wound closure. Unexpectedly, cell area and persistence were found to have the strongest correlation to the observed differences in wound closure. Meanwhile, the model predicted a relatively weak correlation between wound closure with proliferation, and the unexpectedly minor input from proliferation was successfully tested with inhibition by aphidicolin. Combined, these results suggest that the poor clinical results for growth factor-based therapies for chronic wounds may result from a disconnect between the individual cellular behavi...Continue Reading

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Citations

Jan 13, 2018·Annual Review of Biomedical Engineering·Pamela K KreegerKristyn S Masters
Mar 6, 2019·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·MiJung KimChan-Wha Kim
Mar 31, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chloe S KimKristyn S Masters
Aug 8, 2019·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Hyeonjun HongDong Sung Kim
Oct 2, 2019·Bioengineering & Translational Medicine·Chloe S KimPamela K Kreeger
Jul 22, 2019·The Journal of Investigative Dermatology·Leah C BiggsSara A Wickström
Jul 20, 2019·Matrix Biology : Journal of the International Society for Matrix Biology·Anthony J BergerPamela K Kreeger
Jan 1, 2019·ACS Biomaterials Science & Engineering·Catalina-Paula SpatareluZi Chen

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