(6dq) Crowding and Confinement in Fluids and Biological Systems

Mittal, J., National Institute of Health

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, 

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

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.

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].

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.

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.


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.
, 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

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).