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

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 behaviors targeted in these approaches and the resulting collective response. Additionally, the stiffness-dependency of EGF sensitivity suggests that therapies matched to microenvironmental characteristics will be more efficacious.

SUBMITTER: Wickert LE

PROVIDER: S-EPMC4735862 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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

Wickert Lisa E LE Pomerenke Shaun S Mitchell Isaiah I Masters Kristyn S KS Kreeger Pamela K PK

Scientific reports 20160202

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 stiff ...[more]

PMID: 26832302

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Project description:Many species of fish rely on their visual systems to interact with conspecifics and these interactions can lead to collective behavior. Individual-based models have been used to predict collective interactions; however, these models generally make simplistic assumptions about the sensory systems that are applied without proper empirical testing to different species. This could limit our ability to predict (and test empirically) collective behavior in species with very different sensory requirements. In this study, we characterized components of the visual system in two species of cyprinid fish known to engage in visually dependent collective interactions (zebrafish Danio rerio and golden shiner Notemigonus crysoleucas) and derived quantitative predictions about the positioning of individuals within schools. We found that both species had relatively narrow binocular and blind fields and wide visual coverage. However, golden shiners had more visual coverage in the vertical plane (binocular field extending behind the head) and higher visual acuity than zebrafish. The centers of acute vision (areae) of both species projected in the fronto-dorsal region of the visual field, but those of the zebrafish projected more dorsally than those of the golden shiner. Based on this visual sensory information, we predicted that: (a) predator detection time could be increased by >1,000% in zebrafish and >100% in golden shiners with an increase in nearest neighbor distance, (b) zebrafish schools would have a higher roughness value (surface area/volume ratio) than those of golden shiners, (c) and that nearest neighbor distance would vary from 8 to 20 cm to visually resolve conspecific striping patterns in both species. Overall, considering between-species differences in the sensory system of species exhibiting collective behavior could change the predictions about the positioning of individuals in the group as well as the shape of the school, which can have implications for group cohesion. We suggest that more effort should be invested in assessing the role of the sensory system in shaping local interactions driving collective behavior.

Dataset Information

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

Publications

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

Similar Datasets

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