Differential modulation of cellular bioenergetics by poly(l -lysine)s of different molecular weights

Arnaldur Hall, Lin Ping Wu, Ladan Parhamifar, Seyed Moein Moghimi

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2119-2126
Number of pages8
JournalBiomacromolecules
Volume16
Issue number7
DOIs
StatePublished - Jul 13 2015

ASJC Scopus subject areas

  • Bioengineering
  • Materials Chemistry
  • Polymers and Plastics
  • Biomaterials

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