How do cell penetrating peptides enter cells?

• Grant number: 19/03023-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: May 01, 2019
• End date: February 28, 2023
• Field of knowledge: Biological Sciences - Biophysics - Biophysics of Processes and Systems
• Principal Investigator: Iolanda Midea Cuccovia
• Grantee: Peter Park
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08166-5 - Interfacial chemistry: drugs, peptides and ezymes interactions with membrane models, AP.TEM
• Associated scholarship(s): 19/26557-8 - Coarse graining analysis of the interaction of antimicrobial and cell penetrating peptides with lipid vesicles, BE.EP.DD

Abstract

Cell Penetrating Peptides (CPP) invade eukaryotic cells without damaging the plasma membrane. TAT, a widely used CPP, is an intracellular carrier of drugs, proteins and DNA. The CPP penetration mechanism into cells, despite their increasing use, is controversial. Experimental and theoretical findings diverge; a group of authors propose that penetration depends on classic mechanisms such as endocytosis while others propose penetration through direct translocation with no energy need. The elucidation of the penetration mechanism will provide new insights on the understanding of protein/peptide-membrane interactions, as well as contribute to enhance the efficacy and selectivity of the use of TAT as an intracellular transporter. By employing experimental approaches and Molecular Dynamics simulations, this project aims to study the detailed molecular mechanism of action of TAT. TAT analogues with hydrophobic tails will also be used to study the role of hydrophobicity on the interaction of TAT with membranes. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LACERDA, C. D.; JULIANO, M. A.; LIRIA, C. W.; MACHINI, M. T.; PARK, P.; MATSUBARA, D. K.; BARZOTTO, D. R.; LIMA, F. S.; CHAIMOVICH, H.; CUCCOVIA, I. M.. Position matters in ester thiolysis by cysteine-containing peptides in micelles and vesicles. RESULTS IN CHEMISTRY, v. 6, p. 10-pg., 2023-12-01. (19/03023-8, 14/50983-3, 15/10411-3, 22/01825-2, 13/08166-5)

FRANCO, LEANDRO R.; PARK, PETER; CHAIMOVICH, HERNAN; COUTINHO, KALINE; CUCCOVIA, IOLANDA M.; LIMA, FILIPE S.. imulations reveal that antimicrobial BP100 induces local membrane thinning, slows lipid dynamics and favors water penetratio. RSC ADVANCES, v. 12, n. 8, p. 4573-4588, FEB 3 2022. (14/50983-3, 13/08166-5, 19/03023-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

PARK, Peter. How do antimicrobial peptides destroy membranes? A Molecular Dynamics perspective. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.