纳米（生物）通道内水分子的动力学研究：物理、生物意义和应用 Fang Haiping (方海平） Shanghai Institute of Applied Physics Chinese Academy of Sciences (中国科学院上海应用物理研究所) 2018/11/27

Outline Introduction Simulation and results Clear water & nanotechnology/ biological water/anomaly Simulation and results Mechanical and electrical gating (开关特性） Nanochannels inspired by the structures of Aquaprins (水通道蛋白） 3. Summary 2018/11/27

Water shortage threatens humanity particularly in China 水资源短缺威胁人类，特别是中国 Atlas of a thirsty planet 水自给比例 Most of the developing countries : insufficient safe water Nature 422, 252 (2003) 大部分发展中国家缺水

Water Pollution in Taihu Lake : The blue-green algae (蓝藻）outbreak （暴发）in Taihu Lake has affected daily water supply in Wuxi (2007) http://english.cri.cn/4426/2007/06/05/202@235148.htm 2018/11/27

Desalination(水中去盐)— (the process of removing salts and suspended solids from brackish water and seawater) may be best hope to slake world's thirst. New Scientist, 30 June 2006 Problem: high cost Key: Semipermeable membrane to dilute a chemical solution on the other side “Basically, [membrane] technology hasn’t changed much in the last 40 years,” says Thomas Mayer, a desalination expert at Sandia. Desalination plant in Ashkelon, Israel Key part: Channels Science313,1088 (2006); Nature 452, 301 (2008)

Nanotechnology & water http://www.merid.org/nano/waterworkshop Nanotechnology is already being used to remove contaminants from drinking water and increase the availability of fresh water, but there is still a long way to go.----- Hillie and Hlophe, “Nanotechnology and the challenge of clean water”,COMMENTARY, Nature Nanotech. 2, 663 (2007) Nanofluidic 2018/11/27

Nanochannel desalination Key part of the semipermeable membrane---pores, allow fast transportation of water but stops ion permeation Aquaporin---A biological water channel allows water to get in and out of cells but blocks the nimble proton 2003 Noble Prizer in chemistry Single-file water 2018/11/27 Clapham Cell 115,641(2003)

Desalination based on carbon nanotube (CNT) Bio-inspired: Aquaporin is too complex, CNT with appropriate radius can be a good candidate Hummer found, unexpectedly, there are water molecules inside the hydrophobic single-walled carbon nanotube, Nature 414,188（2001） 2018/11/27 水的运动协调一致(向上或向下)

small mechano-sensitive channel MscS Common: Wet-dry transition induced by a minor change of the water-channel interaction small mechano-sensitive channel MscS Hummer, Nature 414,188（2001） Biophys. J. 86,2883 (2004) Water: cyan sticks 2018/11/27

Experimental measurement on water across narrow CNT Enhanced about 1,000 times Holt et al. Science 2006, 312, 1003 Many applications in nanotechnology: desalination of seawater, and the filtration of polluted water. Numerical simulation plays an important role!

Individual Water-Filled Single-Walled Carbon Nanotubes as Hydroelectric Power Converters Chen Wang, Sishen Xie and Lianfeng Sun et al Adv. Mater. 2008,20,1 中科院纳米中心/物理所 Experiment A water flow induced inside the SWNT which is driven by the applied current and causes one part of the device to act as a ‘‘motor’’.

问题 如何控制(生物)水通道内水流的开关? 生物水通道的复杂结构对通道内的水链和水流起什么作用? 机械外力导致形变引起通道的开关 JACS 2005 通道旁边电荷导致的开关 PNAS 2007 生物水通道上电荷分布的意义, 仿照生物水通道电荷分布设计了纳米水泵 Nature Nanotech. 2007 ………… 2018/11/27

Biological Water Confined water is importance on the structures and functions of biomolecules High Humidity B-DNA Low humidity A-DNA DNA conformation Nature 171, 740 (1953)；北师大 Fengshou Zhang PRL100, 088104 (2008) Water-mediated interactions facilitates native-like packing of surpersecondary structural elements of a protein PNAS, 101,3352 (2004) Dynamically ordered water on the surface of DNA PNAS,100, 8113 （2003） Hydrophobic interaction mediates the collapsing of a two-domain protein Science 305, 1605 (2004) 拉直 切割 拾取

水对生物分子的重要性得到认识 水是细胞生物学的活性组分：最近20年左右，有一点越来越清楚，水不是简单的“生命溶剂”，而是以复杂和本质性的方式主动与生物分子发生作用 Nature 顾问编辑（Consultant Editor） Philip Ball综述文章Chemical Reviews 108, 74 (2008) 2018/11/27

Known water Anomalies (异常性质) Unique property of water Known water Anomalies (异常性质) T(K) High melting and boiling temperatures. - They should be lower according to its molecular weight. Density maximum at 4oC (H2O). High heat capacity. Large among energy stored in the system …. 2018/11/27

水是生命之源，但水的特性还没有被完全理解 Science 2004 年度进展 有科学家认为100年来关于液态水的结构可能错了！…别急着修改教科书，最近的同步辐射实验数据支持原来水的结构。 2018/11/27

Water Anomalies originates from hydrogen-bonds between water molecules H-bond network 水的异常性质起源于氢键的存在 2018/11/27

Osmotic pressure (渗透压） up-bottom Mechanical Response R.Z. Wan, J.Y Li, H.Y. Lu, H.P. Fang, J. Am. Chem. Soc. 127, 7166 (2005) A δ B F Osmotic pressure (渗透压） up-bottom Carbon nanotube diameter: 8.1Å length:13.4 Å Carbon nanotube is deformed due to external force F on an atom Effective pore size: 8.1-3.4=4.8Å Water radius: 2.8Å Red: Water molecules, Green: carbon atoms

Simulation results N : Number of water molecules inside the tube Water flux: Difference of the numbers of water molecules entered the SWNT from bottom and upper ends, left on the other sides, per nanosecond . T=216 ns; Transient: 16 ns; flux is averaged by each 18 ns Effective pore size: 4.8Å Water radius: 2.8Å 2018/11/27

Excellent gating！ Effectively resistant to noisy deformation Our Observation Wan等，JACS，2005 Excellent gating！ Effectively resistant to noisy deformation Sensitive to available signals Carbon nanotube Radius= 8.1Å, Length=13.4 Å Osmotic pressure up-bottom Flux（red line）does not decrease N: Number of water molecules inside the channel

Applications (可控纳米器件） Force ≈1.8 nN from open to closed In the force range of many experimental facilities. Possible nanosensor, i.e., nanoscale syringe (注射器） 2018/11/27

形变引起的开关物理机制 一维水链的相邻水分子间氢键类似波形的水分子密度分布 波峰移位抵消碳管形变影响,最大形变位置逐步变到波谷 Wan et al.，JACS，2005 形变引起的开关物理机制 一维水链的相邻水分子间氢键类似波形的水分子密度分布 波峰移位抵消碳管形变影响,最大形变位置逐步变到波谷 转变点最大形变位置成为波谷的δ值 最大形变位置 碳管上碳原子位置 2018/11/27

Biological channels are expected to share this excellent gating due to similar wavelike water density distribution Wan et al，JACS，2005 Wavelike water density distribution in Biological channel GlpF Tajkhorshid et al. Science 2002, 296, 525

Electrical Response How do the charges on Aquporins influence the water permeation? Partial charges here Water chain Tajkhorshid et al. Science 2002, 296, 525

Simulation system Green sphere: the imposed charge. J.Y. Li, H.P. Fang et al, Proc. Natl. Acad. Sci. USA, 104, 3687 (2007). radius= 8.1Å, length=13.4 Å Osmotic（渗透） pressure Green sphere: the imposed charge. 2018/11/27

Excellent gating（开关效应）, too！ Li et al., PNAS, 2007 Excellent gating（开关效应）, too！ Effectively resistant to noisy charge signals Sensitive to available charge signals Flow=all water penetrating through Flux= up – down (for water penetrates through) δ > 0.85 Å : Flux is very close to the system without any charge (dashed)

Why water-charge interaction show local property? φ Dipole z 2018/11/27

Why excellent gating? PCWC: Interaction energy of the water molecule facing the imposed charge with the imposed charge. PCWW : Interaction energy of the water molecule facing the imposed charge with its neighbored water molecules. At the transition point: δ ~ 0.85 Å , PCWC= PCWW Competition: charge-water interaction --- STRONG hydrogen-bonging interactions transition point

Orientation transitoion of water molecules φ Dipole z 2018/11/27

Li et al., PNAS, 2007 PCWW : interaction energy of the water molecule facing the imposed charge with the imposed charge PCWC : interaction energy of the water molecule facing the imposed charge with its neighbored water molecules Flow and the net flux decreases exponentially with respect of (PCWW – PCWC) in the interval of 0.25 Å ≤ δ ≤ 0.75 Å. 2018/11/27

Bipolar  or  water transport In AQPs, the bipolar water order stops proton permeation but not water transport. Net flux = 1.9 /ns (21% of those of the fully opened state), comparable to the measured 3.9 ± 0.6 /ns δ = 0.5 Å

A charge driven molecular water pump inspired by the charge distribution of conserved regions in biological channels called aquaporins X.J. Gong, H.P. Fang et al., Nature Nanotechnology 2, 709 (2007) Net flux 2.8/nanosecond Aquaprins

A charge driven molecular water pump (Why？) Hydrogen bonds in quasi-one-dimensional water chain External charge fields induces definite HB orientations, making water easy to be driven by electric fields A combination of charge makes relative low potential barriers Asymmetry charge distribution drives water from one end to the other end Bottom: only charge left（<0.1/ns) Middle: only two charges middle (0/ns) Main: Our design (2.8/ns) Merged：two partial charges merged into one, larger potential barrier, lower net flux (0.4/ns) 1e 0.5e each

Importance of water orientation distribution on the pumping ability Blue lines: Theoretical predictions of the water-charge interaction potential from the <φ> distribution. Recover the positions of the potential valleys 2018/11/27

Importance of water orientation distribution on the pumping ability Green lines: Theoretical predictions by further taking into the the average position <x> of the water molecules along the channel better 2018/11/27

X.J. Gong, H.P. Fang et al., Nature Nanotechnology 2, 709 (2007) 2, 673 (2007) Water flow Designed Nanopump Schematics of AQP1

Summary Mechanical and electrical gating for narrow nanochannels with single-filed water molecules inside ------ understanding of the mechanics of the biological channels and applications in designing controllable nanochannels Designing of the charge driven molecular water pump inspired by the charge distribution of conserved regions in biological channels called aquaporins. Haiping Fang et al, Dynamics of single-file water chains inside nanoscale channels: physics, biological significance and applications, J. Phys D. (Topical Review) 41, 103002 (2008) 2018/11/27

Thanks you for your attention Acknowledgements Drs. Wan Rongzheng, Lei Xiaoling, Gong Xiaojing, Lu Hangjun at Shanghai Institute of Applied Physics, Chinese Academy of Sciences Dr. Li Jingyuan at Zhejiang University Dr. Zhou Ruhong at IBM, USA Profs. Hu Jun and Fan Chunhai at Shanghai Institute of Applied Physics, CAS 欢迎加入我们研究组 fanghaiping@sinap.ac.cn 2018/11/27 上海同步辐射