Slow Relaxations of Hydration Water near a Lipid Membrane: a Molecular Dynamics Study.

Thumbnail Image
Srivastava, Abhinav
Debnath, Ananya
Journal Title
Journal ISSN
Volume Title
Indian Institute of Technology Jodhpur
Water is the most abundant molecule in cell membranes [1]. Water near membranes affects several biological processes such as transport of drugs and small molecules across the cell, influences formation of membrane rafts [2], molecular recognition and signal transduction [3]. In the past decade, with a major advancement of computer simulations and experimental techniques, water near bio and soft interfaces are found to have distinct properties with slow relaxations compared to that of the bulk water and these water molecules are termed as biological water [4-6]. However, molecular details of biological water from membrane experiments remain fragmentary due to the fluidity of membranes at physiological temperature and atomistic trajectories are still inaccessible. Moreover, the influence of water on global dynamics of membrane or protein are still debated [7-8]. Thus, the current work proceeds to investigate hydration water dynamics near lipid membranes using all atom molecular dynamics simulations to answer few pertinent questions.Capturing structure and dynamics of both lipids and water near membranes using computer simulations as in experiments is a challenging task till date. Thus, we aim to find most relevant water model and lipid force-field to understand dynamics of membrane and hydration layers using all atom molecular dynamics simulations. Dimyristoylphophatidylcholine (DMPC) lipid bilayers have been investigated at fluid phase where water residing continuously within ±3 Ǻ away from the interface are identified as interfacial water (IW). Our investigations show that TIP4P/2005 water model in combination with Berger lipid force field is most suitable to study hydration dynamics near a fluid lipid membrane [9]. IW hydrogen bonded solely among themselves and to carbonyl, phosphate and glycerol head groups of lipids are identified as IW-IW, IW-CO, IW-PO and IW-Glyc respectively. The mean square displacements and the re-orientational autocorrelation functions are slowest for the IW-CO since these are buried deep in the hydrophobic core among all interfacial water. The intermittent hydrogen bond auto-correlation functions of IW show eventual power law behavior of t-3/2 indicating translational diffusion dictated dynamics during hydrogen bond reaking and formation irrespective of the nature of chemical confinement. The analysis suggests that the networks in the hydration layer of membranes dynamically facilitate the water mediated lipid-lipid associations [10]. To find out the physical sources of universal slow relaxations of hydration layers and length-scale of the spatially heterogeneous dynamics, well established formalisms of glass dynamics have been mployed on the IW and the membrane. Two time-scales for the ballistic motions and hopping transitions are obtained from the self intermediate scattering functions of the IW molecules with an additional long relaxation which disappears for bulk water. Employing block analysis approach, the length-scale of dynamical heterogeneities of IW is captured which is comparable to the wavelength of the weak undulations of the membrane. The analysis provides a measure towards spatio-temporal scale of dynamical heterogeneity of confined water near membranes [11]. To gain access in membrane dynamics and its functionality towards various ological processes, investigations are carried out on coupling between hydration layer and bilayer dynamics. The IW molecules exhibit Fickian but intermittent dynamics due to vibrations in the local cage followed by translational jumps with eventual diffusion. Each IW molecule hydrogen bonded to a lipid head vibrates in a cage followed by a translational jump to another cage where it is again hydrogen bonded to another lipid head. The distribution of the logarithm of displacements of the IW shows a bimodal nature which is a characteristic of intermittent behavior leading to dynamical heterogeneity. The differences in regional dynamics of lipid heads are clearly reflected in the spatially resolved IW dynamics gradually from the deeper hydrophobic side to the outermost interface [12].In summary, the work provides insights on the hoice of force fields to apprehend physical laws of water relaxations near membranes. Role of water in membrane associations enables to gain deeper insights on thermodynamic stability of soft interfaces. The current study opens up a possible correlation between heterogeneous length scale and membrane curvature for rippled membranes in future. Our results indicate that hydration water dynamics can act as a sensitive flector of membrane phase and regional membrane dynamics. These will be useful to understand membrane functions such as molecular recognition, binding and domain formation and can contribute to control drug delivery and mimic cryo-preservation techniques for biomedical applications.
Srivastava, Abhinav. (2020). Slow Relaxations of Hydration Water near a Lipid Membrane: a Molecular Dynamics Study (Doctor's thesis). Indian Institute of Technology Jodhpur, Jodhpur.