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

- Conference: AIChE Annual Meeting
- Year: 2007
- Proceeding: 2007 AIChE Annual Meeting
- Group: Education
- Session:
- Time:
Sunday, November 4, 2007 - 3:30pm-6:00pm

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).