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Differential Modulation of Cellular Bioenergetics by Poly(_L -lysine)s of Different Molecular Weights

Lookup NU author(s): Professor Moein MoghimiORCiD

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Abstract

© 2015 American Chemical Society. Poly(l-lysine)s (PLLs), and related derivatives, have received considerable attention as nonviral vectors. High molecular weight PLLs (H-PLLs) are superior transfectants compared with low Mw PLLs (L-PLLs), but suggested to be more cytotoxic. Through a pan-integrated metabolomic approach using Seahorse XF technology, we studied the impact of PLL size on cellular bioenergetic processes in two human cell lines. In contrast to L-PLLs (1-5 kDa), H-PLLs (15-30 kDa) were more detrimental to both mitochondrial oxidative phosphorylation (OXPHOS) and glycolytic activity resulting in considerable intracellular ATP depletion, thereby initiating necrotic-type cell death. The cellular differences to polycation sensitivity were further related to the mitochondrial state, where the impact was substantial on cells with hyperpolarized mitochondria. These medium-throughput approaches offer better opportunities for understanding inter-related intracellular and cell type-dependent processes instigating a bioenergetics crisis, thus, aiding selection (from available libraries) and improved design of safer biodegradable polycations for nucleic acid compaction and cell type-specific delivery.

Publication metadata

Author(s): Hall A, Wu L-P, Parhamifar L, Moghimi SM

Publication type: Article

Publication status: Published

Journal: Biomacromolecules

Year: 2015

Volume: 16

Issue: 7

Pages: 2119-2126

Online publication date: 08/06/2015

Acceptance date: 01/01/1900

ISSN (print): 1525-7797

ISSN (electronic): 1526-4602

Publisher: American Chemical Society

URL: https://doi.org/10.1021/acs.biomac.5b00533

DOI: 10.1021/acs.biomac.5b00533

PubMed id: 26053306

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