The promise of single-cell mechanophenotyping for clinical applications

Abstract

Cancer is the second leading cause of death worldwide. Despite the immense research focused in this area, one is still not able to predict disease trajectory. To overcome shortcomings in cancer disease study and monitoring, we describe an exciting research direction: cellular mechanophenotyping. Cancer cells must overcome many challenges involving external forces from neighboring cells, the extracellular matrix, and the vasculature to survive and thrive. Identifying and understanding their mechanical behavior in response to these forces would advance our understanding of cancer. Moreover, used alongside traditional methods of immunostaining and genetic analysis, mechanophenotyping could provide a comprehensive view of a heterogeneous tumor. In this perspective, we focus on new technologies that enable single-cell mechanophenotyping. Single-cell analysis is vitally important, as mechanical stimuli from the environment may obscure the inherent mechanical properties of a cell that can change over time. Moreover, bulk studies mask the heterogeneity in mechanical properties of single cells, especially those rare subpopulations that aggressively lead to cancer progression or therapeutic resistance. The technologies on which we focus include atomic force microscopy, suspended microchannel resonators, hydrodynamic and optical stretching, and mechano-node pore sensing. These technologies are poised to contribute to our understanding of disease progression as well as present clinical opportunities.

FIG. 1.

Mechanical stimuli and mechanical properties in the metastatic cascade.

FIG. 2.

Technologies that have been applied in the mechanophenotyping of clinical samples and single cells within primary tissues. (a) Piezoresistive microcantilever. Reprinted with permission from Pandya et al. Biosens. Bioelectron., 63, 414–424 (2014), Copyright 2014 Elsevier. (b) Suspended microchannel resonator. Bagnall et al., Sci. Rep., 5, 18542 (2015). Copyright 2015 Author(s), licensed under a Creative Commons Attribution (CC BY 4.0) License. (c) Microfluidic hydrodynamic stretching. Reproduced with permission from Gossett et al. Proc. Natl. Acad. Sci. U.S.A. 109(20), 7630–7635 (2012) Copyright 2012 Author(s). (d) Shear-induced deformability cytometry. Toepfner et al. eLife, 7, e29213 (2018), Copyright 2018 Author(s), licensed under a Creative Commons Attribution (CC BY) License. (e) Mechano node-pore sensing. Kim et al. Microsyst. Nanoeng., 4, 17091 (2018), Copyright 2018 Author(s), licensed under a Creative Commons Attribution (CC BY 4.0) License.