TY - JOUR
T1 - Dynamic intracellular exchange of nanomaterials' protein corona perturbs proteostasis and remodels cell metabolism
AU - Cai, Rong
AU - Ren, Jiayu
AU - Guo, Mengyu
AU - Wei, Taotao
AU - Liu, Ying
AU - Xie, Chunyu
AU - Zhang, Peng
AU - Guo, Zhiling
AU - Chetwynd, Andy
AU - Lynch, Iseult
AU - Ke, Pu Chun
AU - Chen, Chunying
PY - 2022/6/2
Y1 - 2022/6/2
N2 - The nanomaterial–protein “corona” is a dynamic entity providing a synthetic–natural interface mediating cellular uptake and subcellular distribution of nanomaterials in biological systems. As nanomaterials are central to the safe-by-design of future nanomedicines and the practice of nanosafety, understanding and delineating the biological and toxicological signatures of the ubiquitous nanomaterial–protein corona are precursors to the continued development of nano–bio science and engineering. However, despite well over a decade of extensive research, the dynamics of intracellular release or exchange of the blood protein corona from nanomaterials following their cellular internalization remains unclear, and the biological footprints of the nanoparticle–protein corona traversing cellular compartments are even less well understood. To address this crucial bottleneck, the current work screened evolution of the intracellular protein corona along the endocytotic pathway from blood via lysosomes to cytoplasm in cancer cells. Intercellular proteins, including pyruvate kinase M2 (PKM2), and chaperones, displaced some of the initially adsorbed blood proteins from the nanoparticle surface, which perturbed proteostasis and subsequently incited chaperone-mediated autophagy (CMA) to disrupt the key cellular metabolism pathway, including glycolysis and lipid metabolism. Since proteostasis is key to the sustainability of cell function, its collapse and the resulting CMA overdrive spell subsequent cell death and aging. Our findings shed light on the consequences of the transport of extracellular proteins by nanoparticles on cell metabolism.
AB - The nanomaterial–protein “corona” is a dynamic entity providing a synthetic–natural interface mediating cellular uptake and subcellular distribution of nanomaterials in biological systems. As nanomaterials are central to the safe-by-design of future nanomedicines and the practice of nanosafety, understanding and delineating the biological and toxicological signatures of the ubiquitous nanomaterial–protein corona are precursors to the continued development of nano–bio science and engineering. However, despite well over a decade of extensive research, the dynamics of intracellular release or exchange of the blood protein corona from nanomaterials following their cellular internalization remains unclear, and the biological footprints of the nanoparticle–protein corona traversing cellular compartments are even less well understood. To address this crucial bottleneck, the current work screened evolution of the intracellular protein corona along the endocytotic pathway from blood via lysosomes to cytoplasm in cancer cells. Intercellular proteins, including pyruvate kinase M2 (PKM2), and chaperones, displaced some of the initially adsorbed blood proteins from the nanoparticle surface, which perturbed proteostasis and subsequently incited chaperone-mediated autophagy (CMA) to disrupt the key cellular metabolism pathway, including glycolysis and lipid metabolism. Since proteostasis is key to the sustainability of cell function, its collapse and the resulting CMA overdrive spell subsequent cell death and aging. Our findings shed light on the consequences of the transport of extracellular proteins by nanoparticles on cell metabolism.
KW - cell metabolism
KW - chaperone-mediated autophagy
KW - protein corona
KW - proteostasis
UR - http://www.scopus.com/inward/record.url?scp=85131254095&partnerID=8YFLogxK
U2 - 10.1073/pnas.2200363119
DO - 10.1073/pnas.2200363119
M3 - Article
SN - 1091-6490
VL - 119
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 23
M1 - e2200363119
ER -