The long-term objective of this project is to understand how an ion channel called Piezo1 endows living cells with the ability to sense mechanical forces in their environment. This ability underlies a wide range of physiological processes that are essential to life, including the control of cell size and shape, the coalescence of cells into an organ system, and blood pressure control. The experiments are designed on the principle that to understand we must first see what Piezo1 looks like in its various forms. To this end the electron microscope will be used. We must also observe the functional properties of Piezo1 under conditions in which we understand every component present. Then, by comparing the functional properties, that is, how much the channel opens and closes under known quantities of applied force, with the structures, we can construct a physics-based model to explain the observable properties of Piezo1. Because we know that biology is complex, in a final stage of this project we aim to determine structures of Piezo1 in the cell membrane. There, we cannot yet know all the components that are present, but we hope to further understand how the more complex environment of the cell regulates the behavior of Piezo1.

Public Health Relevance

This project seeks to understand how the Piezo1 ion channels endow cells with the ability to sense mechanical forces in their environment. This ability underlies a wide range of physiological processes that are essential to life.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Biochemistry and Biophysics of Membranes Study Section (BBM)
Program Officer
Nie, Zhongzhen
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Rockefeller University
Graduate Schools
New York
United States
Zip Code
Lee, Chia-Hsueh; MacKinnon, Roderick (2018) Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures. Science 360:508-513
Wang, Weiwei; MacKinnon, Roderick (2017) Cryo-EM Structure of the Open Human Ether-à-go-go-Related K+ Channel hERG. Cell 169:422-430.e10
Lee, Chia-Hsueh; MacKinnon, Roderick (2017) Structures of the Human HCN1 Hyperpolarization-Activated Channel. Cell 168:111-120.e11
Tao, Xiao; Hite, Richard K; MacKinnon, Roderick (2017) Cryo-EM structure of the open high-conductance Ca2+-activated K+ channel. Nature 541:46-51
Hite, Richard K; Tao, Xiao; MacKinnon, Roderick (2017) Structural basis for gating the high-conductance Ca2+-activated K+ channel. Nature 541:52-57
Hite, Richard K; MacKinnon, Roderick (2017) Structural Titration of Slo2.2, a Na+-Dependent K+ Channel. Cell 168:390-399.e11
Whicher, Jonathan R; MacKinnon, Roderick (2016) Structure of the voltage-gated K? channel Eag1 reveals an alternative voltage sensing mechanism. Science 353:664-9
Su, Zhenwei; Brown, Emily C; Wang, Weiwei et al. (2016) Novel cell-free high-throughput screening method for pharmacological tools targeting K+ channels. Proc Natl Acad Sci U S A 113:5748-53
Touhara, Kouki K; Wang, Weiwei; MacKinnon, Roderick (2016) The GIRK1 subunit potentiates G protein activation of cardiac GIRK1/4 hetero-tetramers. Elife 5:
Wang, Weiwei; Touhara, Kouki K; Weir, Keiko et al. (2016) Cooperative regulation by G proteins and Na(+) of neuronal GIRK2 K(+) channels. Elife 5:

Showing the most recent 10 out of 59 publications