Mechanobiology

Research Areas

• Structure and function of mechanosensitive ion channels
• Lipid - mechanosensitive channel interactions
• Mechano-electric feedback in the heart
• Mechanosensory transduction in chondrocytes
• Membrane mechanics

Research Overview

Research in the Martinac laboratory focuses on ion-channel mediated mechanosensory transduction processes in living cells from bacteria to humans. Mechanosensitive ion channels have been identified as the primary molecular transducers of mechanical force that function in diverse physiological processes, including touch, hearing, blood pressure regulation and bone development. It has been recognised that aberrant mechanosensitive ion channels contribute to the pathology of disease, including heart dysfunction and osteoarthritis, which are specific research topics the Martinac Laboratory are working on. The laboratory works on these topics because there is currently a limited understanding of the role these ion channels play in causing heart and cardiovascular disease and understanding what happens when heart cells are stretched, for example during heart failure or when a patient has high blood pressure.

Professor Martinac and his team are working on which role mechanosensitive ion channels play in mechano-electrical transduction in chondrocytes, the cells responsible for the homeostatic maintenance of cartilage, a resilient and flexible connective tissue that covers and protects the ends of bones at the joints. In addition, they study bacterial mechanosensitive channels, which have over many years been established as excellent models of molecular mechanisms underlying mechanotransduction in living organisms.

There are 4 key projects underway in the Mechanobiology Laboratory, led by Professor Boris Martinac;

1. Unravelling mechanotransduction pathways in the heart

The aim of this project is to identify a physiological link between cardiac pressure overload and TRP-type ion channels, which may reveal a molecular origin of cardiac remodelling that promotes hypertrophy and arrhythmogenesis.

2. Molecular force sensing mechanisms of Piezo mechanosensitive ion channels

This project focuses on the structure and function of recently identified family of Piezo mechanosensitive channels, which play a crucial role in senses of touch, pain and blood-pressure regulation. The aim of the project is to uncover how different lipids, cytoskeletal proteins and extracellular matrix modulate and alter the function of Piezo channels.

3. Mechanoelectrical transduction in chondrocytes

This project aims to elucidate the contribution of Piezo1 and TRPV4 ion channels to chondrocyte mechanotransduction in mice. It investigates the impact of the cytoskeleton and structure of the extracellular matrix on chondrocyte mechanotransduction to determine the link between the TRPV4/Piezo1-mediated and integrin-mediated mechanotransduction.

4. Biophysics of bacterial MS channels MscL, MscS and MscCG

This project aims to elucidate how mechanosensitive channel proteins of different architecture translate mechanical force transmitted through the membrane lipid bilayer into MS channel protein conformational changes, which is currently an outstanding question of high significance for the mechanotransduction research field.

1. Guo, Y., Yu, Z-Y., Wu, J., Gong, H., Kesteven, S., Iismaa, S.E., Chan, A.Y., Holman, S., Pinto, S., Pironet, A., Cox, C.D., Graham, R.M., Vennekens, R., Feneley, M.P. & Martinac, B. (2021) The Ca2+-activated cation channel TRPM4 is a positive regulator of pressure overload-induced cardiac hypertrophy. eLife 10, e66582.
2. Zhang, Y., Daday, C., Gu, R.-X., Cox, C.D., Martinac, B., de Groot, B.L & Walz, T. (2021) Nature 590 (7846), 509-514.
3. Cox, C.D., Zhang, Y., Zhou, Z., Walz, T & Martinac, B. (2021) Cyclodextrins increase membrane tension and are universal activators of mechanosensitive channels. Proceedings of the National Academy of Sciences USA 118 (36): e2104820118.
4. Romanov, V., Silvani, G., Zhu, H., Cox, C.D. & Martinac, B. (2021) An Acoustic Platform for Single‐Cell, High‐Throughput Measurements of the Viscoelastic Properties of Cells. Small 17(3), 2005759.
5. Ridone, P., Pandzic, E., Vassalli, M., Cox, C. D., Macmillan, A., Gottlieb, P. A., & Martinac, B. (2020). Disruption of membrane cholesterol organization impairs the activity of PIEZO1 channel clusters. The Journal of General Physiology, 152(8).
6. Nikolaev, Y. A., Cox, C. D., Ridone, P., Rohde, P. R., Cordero-Morales, J. F., Vásquez, V., Laver, D.R. & Martinac, B. (2019). Mammalian TRP ion channels are insensitive to membrane stretch. Journal of Cell Science, 132(23).
7. Cox, C. D., Bavi, N., & Martinac, B. (2019). Biophysical Principles of Ion-Channel-Mediated Mechanosensory Transduction. Cell Reports, 29(1), 1-12.
8. Nakayama, Y., Komazawa, K., Bavi, N., Hashimoto, K. I., Kawasaki, H., & Martinac, B. (2018). Evolutionary specialization of MscCG, an MscS-like mechanosensitive channel, in amino acid transport in Corynebacterium glutamicum. Scientific Reports, 8(1): 12893.
9. Ridone, P., Grage, S. L., Patkunarajah, A., Battle, A. R., Ulrich, A. S., & Martinac, B. (2018). “Force-from-lipids” gating of mechanosensitive channels modulated by PUFAs. Journal of the Mechanical Behavior of Biomedical Materials, 79: 158-167.
10. Martinac, A. D., Bavi, N., Bavi, O., & Martinac, B. (2017). Pulling MscL open via N-terminal and TM1 helices: A computational study towards engineering an MscL nanovalve. PLoS ONE, 12(8).
11. Rosholm, K. R., Baker, M. A. B., Ridone, P., Nakayama, Y., Rohde, P. R., Cuello, L. G., Lee, L.K. & Martinac, B. (2017). Activation of the mechanosensitive ion channel MscL by mechanical stimulation of supported Droplet-Hydrogel bilayers. Scientific Reports, 7.
12. Syeda, R., Florendo, M. N., Cox, C. D., Kefauver, J. M., Santos, J. S., Martinac, B., & Patapoutian, A. (2016). Piezo1 Channels Are Inherently Mechanosensitive. Cell Reports, 17(7), 1739-1746.
13. Bavi, N., Cortes, D. M., Cox, C. D., Rohde, P. R., Liu, W., Deitmer, J. W., Bavi, O., Strop, P., Hill, A.P., Rees, D., Corry, B., Perozo, E. & Martinac, B. (2016). The role of MscL amphipathic N terminus indicates a blueprint for bilayer-mediated gating of mechanosensitive channels. Nature Communications, 7.
14. Cox, C. D., Bae, C., Ziegler, L., Hartley, S., Nikolova-Krstevski, V., Rohde, P. R., Ng, C.-A., Sachs, F., Gottlieb, P.A. & Martinac, B. (2016). Removal of the mechanoprotective influence of the cytoskeleton reveals PIEZO1 is gated by bilayer tension. Nature Communications, 7.
15. Nomura, T., Cox, C. D., Bavi, N., Sokabe, M., & Martinac, B. (2015). Unidirectional incorporation of a bacterial mechanosensitive channel into liposomal membranes. FASEB Journal, 29(10), 4334-4345.