Issue 1, 2024

Confinement primes cells for faster migration by polarizing active mitochondria

Abstract

Mechanical cues in the tumor microenvironment interplay with internal cellular processes to control cancer cell migration. Microscale pores present in tumor tissue confer varying degrees of confinement on migrating cells, increasing matrix contact and inducing cytoskeletal rearrangement. Previously, we observed that increased collagen matrix contact significantly increased cell migration speed and cell-induced strains within the matrix. However, the effects of this confinement on future cell migration are not fully understood. Here, we use a collagen microtrack platform to determine the effect of confinement on priming MDA-MB-231 cancer cells for fast migration. We show that migration through a confined track results in increased speed and accumulation of migratory machinery, including actin and active mitochondria, in the front of migrating breast cancer cells. By designing microtracks that allow cells to first navigate a region of high confinement, then a region of low confinement, we assessed whether migration in high confinement changes future migratory behavior. Indeed, cells maintain their speed attained in high confinement even after exiting to a region of low confinement, indicating that cells maintain memory of previous matrix cues to fuel fast migration. Active mitochondria maintain their location at the front of the cell even after cells leave high confinement. Furthermore, knocking out vinculin to disrupt focal adhesions disrupts active mitochondrial localization and disrupts the fast migration seen upon release from confinement. Together, these data suggest that active mitochondrial localization in confinement may facilitate fast migration post-confinement. By better understanding how confinement contributes to future cancer cell migration, we can identify potential therapeutic targets to inhibit breast cancer metastasis.

Graphical abstract: Confinement primes cells for faster migration by polarizing active mitochondria

Supplementary files

Article information

Article type
Paper
Submitted
01 jul 2023
Accepted
07 nov 2023
First published
22 nov 2023
This article is Open Access
Creative Commons BY license

Nanoscale Adv., 2024,6, 209-220

Confinement primes cells for faster migration by polarizing active mitochondria

J. A. Mosier, E. D. Fabiano, C. M. Ludolph, A. E. White and C. A. Reinhart-King, Nanoscale Adv., 2024, 6, 209 DOI: 10.1039/D3NA00478C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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