Multiscale modeling of wound healing Jason Haugh PI

Multiscale modeling of wound healing Jason Haugh PI James Bear co-I Timothy Elston co-I NC State University UNC-Chapel Hill U 01 EB 018816 poster #20

• Cutaneous wounds of a chronic nature affect ~6. 5 million patients in the U. S. • Clinical treatment of these wounds imposes a >$25 billion annual healthcare burden. • ~70 million combined inpatient and outpatient surgeries in the U. S. each year create a huge need for better post-surgical wound care. • Normal wound healing and tumor invasiveness intersect in the context of cancer surgery.

The wound healing cascade Mikael Häggström

The wound healing cascade Mikael Häggström

The wound healing cascade Mikael Häggström

The wound healing cascade Mikael Häggström Martin, Science, 276: 75 (1997)

Directed migration of mesenchymal cells Bear & Haugh, Curr Opin Cell Biol (2014)

Wound healing as a multiscale process

Wu et al. , Cell (2012) Welf et al. , J Cell Biol (2012) Welf et al. , Mol Biol Cell (2013) Bear and Haugh, Curr Opin Cell Biol (2014) Tsygankov et al. , J Cell Biol (2014) Asokan et al. , Dev Cell (2014) Rotty et al. , Dev Cell (2015) Johnson et al. , J Cell Biol (2015) Haynes et al. , J Cell Biol (2015)

Experimental capabilities • Microfluidic chemotaxis assay • High-res imaging/morphodynamics • Analysis of cytoskeletal organization • Intravital imaging (fluoresence/SHG)

Aim 1 (molecular scale): Live-cell microscopy integrated with kinetic modeling to elucidate and characterize amplification mechanisms in PDGF gradient sensing

Aim 1 modeling What are the feedback mechanisms governing amplification of DAG gradients?

Aim 1 modeling • MARCKS dynamics are sufficient to amplify the pathway. • MARCKS synergizes with other feedbacks.

Aim 2 (supramolecular scale): Live-cell microscopy integrated with physicochemical modeling to elucidate mechanisms required for self-assembly of actomyosin structures

Aim 2 modeling • Regulation of motor-filament binding explains the effect of myosin II deactivation

Aim 2 modeling • Organization of actomyosin with graded binding rate