Nanoscale Tracking Combined with Cell-Scale Microrheology Reveals Stepwise Increases in Force Generated by Cancer Cell Protrusions

Luka Sikic, Ester Schulman, Anna Kosklin, Aashrith Saraswathibhatla, Ovijit Chaudhuri*, Juho Pokki*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

9 Citations (Scopus)
98 Downloads (Pure)

Abstract

In early breast cancer progression, cancer cells invade through a nanoporous basement membrane (BM) as a first key step toward metastasis. This invasion is thought to be mediated by a combination of proteases, which biochemically degrade BM matrix, and physical forces, which mechanically open up holes in the matrix. To date, techniques that quantify cellular forces of BM invasion in 3D culture have been unavailable. Here, we developed cellular-force measurements for breast cancer cell invasion in 3D culture that combine multiple-particle tracking of force-induced BM-matrix displacements at the nanoscale, and magnetic microrheometry of localized matrix mechanics. We find that cancer-cell protrusions exert forces from picoNewtons up to nanoNewtons during invasion. Strikingly, the protrusions extension involves stepwise increases in force, in steps of 0.2 to 0.5 nN exerted from every 30 s to 6 min. Thus, this technique reveals previously unreported dynamics of force generation by invasive protrusions in cancer cells.
Original languageEnglish
Pages (from-to)7742-7750
Number of pages9
JournalNano Letters
Volume22
Issue number18
Early online date11 Aug 2022
DOIs
Publication statusPublished - 28 Sept 2022
MoE publication typeA1 Journal article-refereed

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