Molecular Determinants of the Cellular Entry of Asymmetric Peptide Dendrimers and Role of Caveolae

PloS One
Prarthana V RewatkarMarie-Odile Parat

Abstract

Caveolae are flask-shaped plasma membrane subdomains abundant in most cell types that participate in endocytosis. Caveola formation and functions require membrane proteins of the caveolin family, and cytoplasmic proteins of the cavin family. Cationic peptide dendrimers are non-vesicular chemical carriers that can transport pharmacological agents or genetic material across the plasma membrane. We prepared a panel of cationic dendrimers and investigated whether they require caveolae to enter into cells. Cell-based studies were performed using wild type or caveola-deficient i.e. caveolin-1 or PTRF gene-disrupted cells. There was a statistically significant difference in entry of cationic dendrimers between wild type and caveola-deficient cells. We further unveiled differences between dendrimers with varying charge density and head groups. Our results show, using a molecular approach, that (i) expression of caveola-forming proteins promotes cellular entry of cationic dendrimers and (ii) dendrimer structure can be modified to promote endocytosis in caveola-forming cells.

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Citations

Dec 1, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chi-On ChanSibao Chen
May 6, 2020·International Journal of Molecular Sciences·Michał GorzkiewiczBarbara Klajnert-Maculewicz
Aug 21, 2019·Bioconjugate Chemistry·Sameer DhawanV Haridas
Mar 14, 2016·ACS Biomaterials Science & Engineering·Prarthana V RewatkarMarie-Odile Parat

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Methods Mentioned

BETA
dynamic light scattering
fluorescence imaging
fluorescence microscopy
fluorescence imaging microscopy
confocal microscopy
transfection

Software Mentioned

GraphPad Prism
image J
MassLynx TM

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