Mechano-Sensitive Ion Channels (MSCS) Provide Human Breast Cancer Cells with a Sensorium for Mechanical Stress

Abstract

Mechanical stress is increasingly recognized as a cancerogenic factor in breast cancer. We investigated the biophysical characteristics of mechano-sensitive channels (MSCs) in the breast cancer cell line MCF7 with patch clamp methods.MSCs were present in 132 out of 258 cell-attached membrane patches. MSCs could be activated by negative pressure at the outer side of the membrane in a saturable manner (EP50: 41.2 ± 0.5 mbar (N=13).When K+ was predominantly present in the extracellular pipette solution, single channel conductance exerted to be 25.6± 0.4 pS (N=8). When complete ion selectivity was assessed, conductivity was found to increase in the following order: Li+ < Na+ < K+≈Rb+ ≈ Cs+. Furthermore, conductivity was smaller for divalent cations (100 mmole/L compared to 153 mmole/L) with the order: Ca2+ < Ba2+ < K + ≈ Rb + ≈ Cs +. We compared the biophysical properties of MSCs with a recently discovered mechanosensitive cation channel, the human Piezo1 protein, heterologously overexpressed in HEK293 cells. Single channel conductances were indistinguishable between MSCs from MCF7 and hPiezo1 in HEK293 cells, both when 100% K + and 50% K + / 50% Na + were used as permeant ions.MSCs occur in MCF7 breasts cancer cells, providing a sensorium for mechanical stress. Ion selectivity studies show that divalents like Ca2+ can permeate to a considerable extend. Moreover, permeation of monovalents is apparently restricted by the size of the ions hydrate shell, as indicated by the smaller conductivities for Na + and Li +, respectively, indicating that the ion permeation mechanism through MSCs may be different to the cation channels crystallized so far.This research is supported by grants from the Austrian Research Foundation (FWF22974 (WS); KLIF182 (TB)).