How does touch come about?Tsinghua University cracked the unsolved mystery of the Nobel Prize achievement, on the Nature

2022-06-08 0 By

Abundant color number from the sunken the temple qubits | public QbitAI when you brush your phone, to shake hands with others, or stepped on a restrict stone, have you ever wondered: exactly how our bodies feel relevant force?More specifically, how are these physical stimuli converted into bioelectrical signals?This, in fact, is a Problem that even Nobel Prize winners have not figured out.However, it has now been cracked by Tsinghua University!The results are in the latest issue of Nature: Take a look.Nobel Prize mystery: How to feel Mechanical Forces?In fact, the receptor protein for how humans perceive mechanical force was discovered in 2010: PIEZO (Greek for “stress”).The 2021 Nobel Prize in Physiology or Medicine went to Ardem Patapoutian, a Lebanese-born American molecular biologist and neuroscientist.But for more than a decade, the world has yet to figure out exactly how the protein generates a bioelectrical signal when stressed.Because PIEZO is stimulated for such a long time, the technical term is a trimer, three-bladed propeller structure.It is speculated that the central channel is responsible for ion permeability, and the outer blade is responsible for mechanical force perception.When the membrane tension changes, PIEZO changes from a closed state to the flat shape shown in the image above, driving the opening of the central pore, thus converting the mechanical force stimulation into cation flow.Is it really so?Researchers at Tsinghua University set out to find out.In general, cryo-electron microscopy is required to analyze the structure of biological macromolecules.Then came the biggest problem: how to introduce invisible forces in the frozen sample state to obtain the two different states of the supposed PIEZO?After continuous thinking, Tsinghua University borrowed from predecessors to reassemble membrane proteins into liposomes (a kind of thing with the same structure as skin cell membrane) in two different ways, through the difference in curvature between protein and liposome (the higher the value, the greater the degree of curvature of the curve) to introduce membrane tension.What you mean?PIEZO1 (a member of the PIEZO family) itself has a radius of curvature of nearly 10nm and is round in size without deformation in a liposome of the same size.When it reassembles in an outside-in fashion into a larger liposome, the difference in radius of curvature creates forces between the two, and the protein and membrane deform, with the protein in droplet form (first row below).In outside-out, PIEZO1 faces the opposite curvature radius of the protein and the liposome, causing displacement between the membrane and the protein to increase and PIEZO1 flattening out (second row).In the end, the researchers found that PIEZO1 constricted on the membrane and that PIEZO1 flattened, supporting the idea.PIEZO1, or PIEZO1, is reversible and piezopiezo1 formed by piezopiezo1, or PIEZO1, in motion.More closely, they revealed how PIEZO1, which contains piezopiezo1, uses its nanoscale curvature deformation to detect the force at the pyro scale (1pN= 10-12n), becoming a kind of low-energy super-sensitive mechanical force sensor.And this makes the author can not help but marvel at the beauty of the intersection of life process and physical principle!In simple terms, in the resting state, the protein is in equilibrium (bowl surface area is 628nm2, projection area is 314nm2);When the membrane tension changes, the equilibrium is broken and PIEZO1 flattens out with the membrane.At the end of the day, you might wonder, what’s the use of studying it?PIEZO has a wide range of physiological and pathological functions (in the cardiovascular system, cardiac muscle cells, and the formation and remodeling of bone), and understanding its mechanisms allows for drug design.The author introduces the co-authors of this paper, Yang Xuzhong, Lin Chao, Chen Xudong and Li Shouqing, PhD students from Tsinghua University and UNIVERSITY of Science and Technology of China.The corresponding authors are Professor Xiao Baolong and Researcher Li Xueming, School of Pharmacy, Tsinghua University.Baolong Xiao received his bachelor’s degree in biochemistry from Sun Yat-sen University and his PhD from The University of Calgary in Canada. He spent five years as a postdoctoral fellow at Scripps Research Institute in the United States, helping to promote the discovery and research of PIEZO.Currently, he is a professor and doctoral supervisor of the School of Pharmacy, Tsinghua University. He is the recipient of the National Science Fund for Distinguished Young Scholars.Xueming Li received his master’s degree from University of Science and Technology Beijing, PhD from Institute of Physics, Chinese Academy of Sciences, and spent four years as a postdoctoral researcher at UNIVERSITY of California, San Francisco.He is currently an adjunct professor at the School of Life Sciences, Tsinghua University, and a research fellow at the Tsinghua and Peking University Joint Center for Life Sciences, Advanced And Advanced Innovation Center for Structural Biology, and Frontier Research Center for Biological Structures.In recent years, many techniques such as deep learning and particle filtering have been introduced into cryo-electron microscopy.Bailong xiao and Xueming Li have been working together on PIEZO proteins for many years and have published several results before this one.Delta source WeChat at the tsinghua university school of medicine, public figure more details about the study, welcome interested readers to view the original ~ papers address: reference links: