Arginine-rich cell-penetrating peptides.
Arginine-rich cell-penetrating peptides are short cationic peptides capable of traversing the plasma membranes of eukaryotic cells. While successful intracellular delivery of many biologically active macromolecules has been accomplished using these peptides, their mechanisms of cell entry are still under investigation. Recent dialogue has centered on a debate over the roles that direct translocation and endocytotic pathways play in internalization of cell-penetrating peptides. In this paper, we review the evidence for the broad range of proposed mechanisms, and show that each distinct process requires negative Gaussian membrane curvature as a necessary condition. Generation of negative Gaussian curvature by cell-penetrating peptides is directly related to their arginine content. We illustrate these concepts using HIV TAT as an example.
Schmidt
Nathan
N
Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Mishra
Abhijit
A
Lai
Ghee Hwee
GH
Wong
Gerard C L
GC
D000818:Animals; D001120:Arginine / Q000737:chemistry*; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D003198:Computer Simulation; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D004705:Endocytosis / Q000502:physiology; D005057:Eukaryotic Cells / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D016011:Normal Distribution; D010446:Peptide Fragments / Q000737:chemistry* / Q000493:pharmacokinetics*; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000493:pharmacokinetics
D004337:Drug Carriers; D010446:Peptide Fragments; D054322:tat Gene Products, Human Immunodeficiency Virus; D001120:Arginine