The smooth functioning of a biological system depends sensitively on macromolecular transport, facilitating every process from protein transcription to the enzymes finding their target binding sites. One of the distinctive features of these systems is the presence of high molecular concentrations, commonly termed macromolecular crowding. As a manifestation of this crowding and confinement, the behavior of proteins and other intracellular organisms can deviate sharply from that in homogeneous bulk solution. A viable conceptual starting point to understand these deviations is to study how controlled modifications in the model cellular systems will cause a change in the properties of biological macromolecules. This question of understanding the effect of confinement also has parallels in liquid state theories where one is interested in knowing structure, dynamics and thermodynamics as a function of the physical and chemical characteristics of the confining medium.
Currently, I am a postdoctoral fellow in the Laboratory of Chemical Physics, National Institute of Health, Bethesda. The main objective of our research here is to design theoretical and simulation methods to predict the effects of macromolecular crowding and confinement on the protein stability. We are also developing theoretical methods based on path-integral formalism to understand the dominant folding pathways in the helix-coil transition for proteins. This particular approach has advantages over the conventional molecular simulation techniques in treating much longer time and length scales.
In my PhD dissertation, under the supervision of Dr. Thomas M. Truskett and in collaboration with Dr. Jeffrey R. Errington, we focused on understanding equilibrium and supercooled fluid behavior in diverse types of confining environments, starting from the most basic slit-pore model to more realistic quenched-annealed models for porous media. Some of the important findings from these studies are,
(i) The relationship between excess entropy (with respect to ideal gas state) and self-diffusivity for simple fluids is essentially unaffected by confinement, which allows one to use thermodynamics to "predict" how confinement impacts dynamics [1,2,3]. We also have clarified which definition of average density, based on total volume or particle center accessible volume, is most appropriate for understanding the thermodynamic and kinetic effects of confinement.
(ii) A new equation is proposed for predicting fluid diffusivity in "quenched annealed" models for random porous media [4]. Interestingly, it only requires as input the value of bulk fluid diffusivity and the available space in the system, the latter of which is a well defined thermodynamic quantity and therefore possible to calculate exactly. This work contributes toward resolving a controversy in the field regarding whether "static structure" alone can account for the large differences in dynamics by quenched-annealed systems with indistinguishable pair correlation functions.
(iii) We provided evidence that there is an intimate relationship between excess entropy and the self-diffusivity of supercooled liquids. Given that the reduced transport properties of fluids above their freezing point show a quasi-universal scaling with excess entropy, our simulations suggest that the connection between thermodynamics and dynamics exists across the entire liquid range, from ideal gas to glass [5,6].
(iv) The missing link between the structure and mobility of glass-forming liquids in deeply supercooled state is demonstrated to be much simpler (only requires the knowledge of pair correlation function and number density) and broader in context (even valid for systems with anomalous diffusion behaviour such as water models, short-range attractive colloidal system) than previously anticipated [6,7]. It is intimately connected to the two-body excess entropy discussed above.
(v) An "energy landscape based" statistical mechanical theory for nanoscale amorphous films was developed which is based on our hypothesis that the confinement induced shift in the properties of material can be understood in terms of how its energy landscape is changed with respect to the bulk. The theory is able to successfully reproduce several nontrivial experimental trends observed for liquid and glassy films such as shift in bulk thermodynamic phase boundaries, shift in glass transition temperature due to confinement, etc. This landscape based approach is different from current theories in that one can study the thermal, mechanical, and kinetic behavior of a material within the same framework [8].
In my Master's dissertation under the supervision of Prof. Ashutosh Sharma (IIT, Kanpur), we proposed a new mechanism of thin film instability engendered solely by the density variations (for example, due to confinement, layering, defects, and restructuring) that shows the same morphological characteristics as well-known spinodal dewetting [9,10]. This work was aimed at helping a rational design and interpretation of thin film experiments as inverse problem of determining thin film potential from the measurement of instability length scale is shown to be dependent on the uncertainty of density variations.
References
1. J. Mittal, J. R. Errington and T. M. Truskett, "Thermodynamics Predicts How Confinement Modifies Hard-Sphere Dynamics", Phys. Rev. Lett. 96, 177804 (2006).
2. J. Mittal, J. R. Errington, and T. M. Truskett, "Does confining the equilibrium hard-sphere fluid between hard walls change its average properties?" J.Chem. Phys. (submitted)
3. J. Mittal, J. R. Errington, and T. M. Truskett, "Relationships between self-diffusivity, packing fraction, and excess entropy in simple bulk and confined fluids", J. Phys. Chem. B (submitted).
4. J. Mittal, J. R. Errington and T. M. Truskett, "Using Available Volume to Predict Fluid Diffusivity in Random Media", Phys. Rev. E 74, 040102(R) (2006).
5. J. Mittal, J. R. Errington and T. M. Truskett, "Relationship between Thermodynamics and Dynamics of Supercooled Liquids", J. Chem. Phys. 125, 076102 (2006).
6. J. R. Errington, T. M. Truskett, and J. Mittal, "Family of entropy based anomalies for a water-like fluid" J. Chem. Phys. 125, 244502 (2006).
7. J. Mittal, J. R. Errington, and T. M. Truskett, "Quantitative link between single-particle dynamics and static structure if supercooled liquids" J. Phys. Chem. B Letters 110, 18147 (2006).
8. J. Mittal, P. Shah, and T. M. Truskett, "Using energy landscapes to predict the properties of thin films" J. Phys. Chem. B 108, 19769 (2004).
9. A. Sharma and J. Mittal, "Instability of Thin Liquid Films by Density Variations: A New Mechanism that Mimics Spinodal Dewetting", Phys. Rev. Lett. 89, 186101 (2002).
10. A. Sharma, J. Mittal and R. Verma, "Instability and dewetting of thin films induced by density variations", Langmuir 18, 10213-10220 (2002).