Nanoparticles for Fidgety Cell Movement and Enhanced Wound Healing.
Complex spatiotemporal interaction of Rho GTPases with microtubules (MTs) and MT-associated proteins drives directed cellular migration. In this issue, Charafeddine et al. describe a role for a novel MT-severing enzyme, fidgetin-like 2 (FL2), in directional migration of keratinocytes and fibroblasts. FL2 normally localizes to the leading edge of the cell cortex where it shears MTs, thus dictating the size and distribution of focal adhesions by regulating cytoskeletal remodeling. Small interfering RNA (siRNA)-directed knockdown of FL2 increases cell migration and focal adhesion area in vitro through possible interaction with Rho GTPases. Efficient FL2 knockdown in murine wounds was achieved using nanoparticles as a siRNA delivery vehicle, and this resulted in enhanced wound closure in vivo. Effective siRNA nanoparticle targeting of MT-severing enzymes offers promise of controlled and targeted delivery that may maximize therapeutic success for patients with burn wounds and chronic wound disorders.
Wound Healing and Regenerative Medicine Research Program, Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
Ivan
I
Jozic
Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida, USA; Dr JT Macdonald Biomedical Nanotechnology Institute, University of Miami, Miami, Florida, USA.
Sylvia
S
Daunert
Wound Healing and Regenerative Medicine Research Program, Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
Marjana
M
Tomic-Canic
Wound Healing and Regenerative Medicine Research Program, Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA. Electronic address: IPastar@miami.edu.
Irena
I
Pastar
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D008870:Microtubules / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000378:metabolism*
D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D000251:Adenosine Triphosphatases