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|Intracellular Mechanical Drugs Induce Cell-Cycle Altering and Cell Death
|Arjona, María Isabel
Hernández-Pinto, Alberto M.
Agusil, Juan Pablo
Gómez Martínez, Rodrigo
Pérez García, M. Lluïsa (Maria Lluïsa)
Plaza, José Antonio
|Current advances in materials science have demonstrated that extracellular mechanical cues can define cell function and cell fate. However, a fundamental understanding of the manner in which intracellular mechanical cues affect cell mechanics remains elusive. How intracellular mechanical hindrance, reinforcement, and supports interfere with the cell cycle and promote cell death is described here. Reproducible devices with highly controlled size, shape, and with a broad range of stiffness are internalized in HeLa cells. Once inside, they induce characteristic cell-cycle deviations and promote cell death. Device shape and stiffness are the dominant determinants of mechanical impairment. Device structural support to the cell membrane and centering during mitosis maximize their effects, preventing spindle centering, and correct chromosome alignment. Nanodevices reveal that the spindle generates forces larger than 114 nN which overcomes intracellular confinement by relocating the device to a less damaging position. By using intracellular mechanical drugs, this work provides a foundation to defining the role of intracellular constraints on cell function and fate, with relevance to fundamental cell mechanics and nanomedicine. Keywords: biomaterials; cell cycle; mechanobiology; nanomaterials; nanomedicine; silicon chips.
|Versió postprint del document publicat a: https://doi.org/10.1002/adma.202109581
|It is part of:
|Advanced Materials, 2022, p. 2109581
|Appears in Collections:
|Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
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