# Heteropolymers in a Solvent at an Interface

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## Abstract

Exact bounds are obtained for the quenched free energy of a polymer with random hydrophobicities in the presence of an interface separating a polar from a non polar solvent. The polymer may be ideal or have steric self-interactions. The bounds allow to prove that a “neutral” random polymer is localized near the interface at any temperature, whereas a “non-neutral” chain is shown to undergo a delocalization transition at a finite temperature. These results are valid for a quite general a priori probability distribution for both independent and correlated hydrophobic charges. As a particular case we consider random AB-copolymers and confirm recent numerical studies.

PACS numbers: 61.41.+e, 05.40.+j, 36.20.-r

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The statistical behavior of heteropolymers has been intensively studied in recent years . They model random copolymers  and to some extent protein folding . For example, a chain composed by hydrophobic and hydrophilic (polar or charged) components in a polar (aqueous) solvent evolves toward conformations where the hydrophobic part are buried in order to avoid water, wheras the polar part is mainly exposed to the solvent . This is what commonly happens to proteins and makes them soluble in aqueous solutions. However other proteins (e.g. structural proteins) are almost insoluble under physiological conditions and prefer to form aggregates . Many of the proteins which are insoluble in water are segregated into membranes which have a lipid bilayer structure . Membrane proteins have a biological importance at least as great as those which are water soluble. Usually one distinguishes integral and non integral membrane proteins according to whether the protein is most immersed in the lipid bilayers or simply anchored to the membrane respectively (in the latter case the protein is essentially water soluble) . An analogous situation occurs for copolymers at interfaces separating two immiscible fluids. If the solvents are selective (i.e. poor for one of the two species and good for another), AB-copolymers are found to stabilize the interface . Moreover, random copolymers have been claimed to be more effective in carrying out this re-enforcement action .

The simplest theoretical approach to the above problems has been proposed by Garel et al. . In the case of membrane proteins the finite layer of lipidic environment is modeled as an infinite semi-space. Though a quite rough approximation, this is the simplest attempt in capturing the relevant features due to the competition of different selective effects .

We will study a lattice discretized version of their model. The nodes of an $`N`$ links chain occupy the sites $`\stackrel{}{r}_i=(x_{i1},\mathrm{},x_{id})`$, $`i=0,\mathrm{},N`$ of a $`d`$-dimensional hypercubic lattice. A flat interface passing through the origin and perpendicular to the $`\stackrel{}{u}=(1,\mathrm{},1)`$ direction separates a polar (e.g. water), on the $`\stackrel{}{u}\stackrel{}{r}>0`$ side, from a nonpolar (e.g. oil or air), on the $`\stackrel{}{u}\stackrel{}{r}<0`$ side, solvent. The $`i`$-th monomer interacts with the solvent through its hydrophilic charge $`q_i>0`$ ($`q_i<0`$ means that it is hydrophobic) and contributes to the energy with a term $`q_i\mathrm{sgn}(\stackrel{}{u}\stackrel{}{r}_i)`$ . For simplicity we can associate the charge to the link between adjacent positions on the chain instead that to the single monomer.

The partition function of the model for a chain $`W`$ starting at position $`\stackrel{}{r}`$ is

$$𝒵(\stackrel{}{r},\{q_i\})=\underset{W:\stackrel{}{r}.}{}\mathrm{exp}\left\{\beta \underset{i=1}{\overset{N}{}}q_i\mathrm{sgn}(\stackrel{}{u}\stackrel{}{r}_i)\right\},$$
(1)   
where $`\beta ^1=k_BT`$. If one sums over non-interacting (ideal) chains, then the lattice version of the model introduced in Ref.  is recovered. We will consider also the more physical case where steric interaction among monomers does not allow for multiple occupancy of lattice nodes, studied for a particular case in Ref. .

The free energy density of the system reads $`f(\stackrel{}{r},\beta )=lim_N\mathrm{}\frac{1}{\beta N}\overline{\mathrm{ln}𝒵(\stackrel{}{r},\{q_i\})}`$, where $`\overline{\mathrm{}}`$ denotes the quenched average over the distribution of the charges $`\{q_i\}`$. In the following we will assume that $`\{q_i\}`$ are independent random variables having a Gaussian distribution of the form

$$P(q_i)=\frac{1}{\sqrt{2\pi \mathrm{\Delta }^2}}\mathrm{exp}\left[\frac{(q_iq_0)^2}{2\mathrm{\Delta }^2}\right].$$
(2)   
More general cases will be treated at the end. In particular considering charges not independently distributed is of interest for designed sequences as happens for real proteins.

We will show that for a neutral chain ($`q_0=0`$) $`f(0,\beta )<f(\stackrel{}{r},\beta )`$ with $`|\stackrel{}{r}|N`$, in the large $`N`$ limit, and for all $`\beta `$. The same holds also for $`q_00`$ if $`\beta >\beta _{upper}(|q_0|,\mathrm{\Delta })`$ with $`\beta _{upper}0`$ if $`\frac{|q_0|}{\mathrm{\Delta }}0`$. This implies that the chain is localized around the interface at any temperature if $`q_0=0`$, and at sufficently low temperature if $`q_00`$. The proof is rigorous for the ideal chain, whereas for the self-avoiding case only a mild and well accepted hypothesis on the asymptotic behavior of the entropy is needed. When $`q_00`$ a rigorous lower bound on the free energy for both the ideal and the self-avoiding chain allows to determine a $`\beta _{lower}(|q_0|,\mathrm{\Delta })`$ below which the chain is delocalized.

We will first consider the ideal chain case and then explain the modifications necessary to extend the results to self-avoiding chains.

Ideal chain. For clarity we derive the bounds in the $`d=1`$ case. The general case does not contain any further difficulty . Let us first consider initial positions far from the interface in the favorable solvent, $`xN`$ if $`q_0>0`$ or $`xN`$ if $`q_0<0`$. Under these assumptions all chains remain in the same side, implying that $`\mathrm{sgn}\left(x_i\right)=1`$ (or $`\mathrm{sgn}\left(x_i\right)=1`$ respectively) for all $`i`$. Upon averaging over the charge distribution, we obtain the free energy density of a walk in the favorable solvent:

$$f^{}=\frac{1}{\beta }\mathrm{ln}2|q_0|.$$
(3)   
We give an upper bound to the free energy as follows. Consider only chains made up of blobs of $`k`$ steps, with $`k`$ even. Bringing a blob in its globally favored side leads to an energy contribution of the form $`H_{j\mathrm{th}\mathrm{blob}}=\left|_{i=1}^kq_{k(j1)+i}\right|`$, so that

$$𝒵(x=0,\{q_i\})\left(C_k\right)^{\frac{N}{k}}\mathrm{exp}\left\{\beta \underset{j=1}{\overset{\frac{N}{k}}{}}\left|\underset{i=1}{\overset{k}{}}q_{k(j1)+i}\right|\right\},$$

where $`C_k`$ is the number of chains starting and ending in the origin and remaining in the same side. In the one-dimensional case it is easy to exactly determine $`C_k`$. It turns out $`C_k={\displaystyle \frac{1}{\frac{k}{2}+1}}\left(\begin{array}{c}k\\ \frac{k}{2}\end{array}\right)`$, so that, by using the Stirling’s formula, the asymptotic result $`C_k2^kk^{\frac{3}{2}}`$ is found (in $`d`$ dimensions $`C_k(2d)^kk^{\frac{d+2}{2}}`$ ). The upper bound on the free energy is then:

$$f(0,\beta )\frac{1}{\beta }\frac{\mathrm{ln}C_k}{k}\frac{1}{k}\overline{\left|\underset{i=1}{\overset{k}{}}q_i\right|},$$
(4)   
and, by using Eq. (2), we obtain:

$`\mathrm{\Delta }f`$ $`=`$ $`f(0,\beta )f^{}h_{q_0}(k,\beta )`$ (5)   
$``$ $`{\displaystyle \frac{1}{\beta }}\left[\mathrm{ln}2{\displaystyle \frac{\mathrm{ln}C_k}{k}}\right]|q_0|G\left({\displaystyle \frac{\sqrt{k}|q_0|}{\sqrt{2}\mathrm{\Delta }}}\right),`$ (6)   
where the scaling function $`G`$ is given by

$$G(x)=\frac{1}{\sqrt{\pi }}\frac{1}{x}e^{x^2}[1\mathrm{erf}(x)].$$
(7)   
$`G(x)`$ is a positive decreasing monotonic function for positive arguments.

We consider separately the neutral and the $`q_00`$ cases. In the neutral case it turns out that the chain is always localized at the interface. In fact, if $`q_0=0`$ we have

$$\mathrm{\Delta }fh_0(k,\beta )=\frac{1}{\beta }\left[\mathrm{ln}2\frac{\mathrm{ln}C_k}{k}\right]\sqrt{\frac{2}{\pi }}\mathrm{\Delta }\frac{1}{\sqrt{k}}.$$
(8)   
It is easy to see that for any $`\beta `$ there exists a value $`k(\beta )`$ such that $`h_0(k,\beta )<0`$ for $`k>k(\beta )`$. For example at high temperature $`k(\beta )\left[\mathrm{ln}\left(\beta \mathrm{\Delta }\right)\right]^2(\beta \mathrm{\Delta })^2`$. This shows that at any temperature a neutral random chain is always adsorbed by the interface.

In the non-neutral case with $`k=2`$, one has $`\mathrm{\Delta }f<0`$ if

$$\beta >\beta _{upper}=\frac{\mathrm{ln}2}{|q_0|G(\frac{|q_0|}{\mathrm{\Delta }})}.$$
(9)   
The limit $`lim_k\mathrm{}h_{q_0}(k,\beta )=0_+`$ does not allow to deduce the existence of a negative minimum in $`k`$, so that the previous argument, showing that the neutral chain is always localized, does not hold for $`q_00`$. Equation (9) proves localization at sufficiently low temperatures. For $`|q_0|\mathrm{\Delta }`$, it yields $`\beta _{upper}=\frac{\sqrt{\pi }\mathrm{ln}2}{\mathrm{\Delta }}`$, and in the opposite regime $`\mathrm{\Delta }|q_0|`$, $`\beta _{upper}=2\sqrt{\pi }\mathrm{ln}2e^{\frac{|q_0|^2}{\mathrm{\Delta }^2}}\frac{|q_0|^2}{\mathrm{\Delta }^3}`$. In the limit $`|q_0|/\mathrm{\Delta }1`$ we can give a better estimate for $`\beta _{upper}`$, such that $`\beta _{upper}0`$ as $`|q_0|0`$, by considering a larger blob size $`k=2x_0^2\left(\mathrm{\Delta }/|q_0|\right)^2`$, where $`x_0|q_0|/\mathrm{\Delta }`$ is fixed:

$$\beta _{upper}=\frac{3}{2x_0^2G(x_0)}\mathrm{ln}\left(\sqrt{2}x_0\mathrm{\Delta }/|q_0|\right)\frac{|q_0|}{\mathrm{\Delta }^2}.$$
(10)   
We now look for a lower bound on $`f`$ for all chain initial positions. If, for example, $`q_0>0`$, the preferred side is the right one. Consider then the starting point at $`x=Nk`$ ($`0<kN`$) and let $`g_E`$, with $`E`$ some subset of the last $`k`$ steps of the walk ($`0<|E|k`$ with $`|E|`$ the number of elements in $`E`$), be the number of walks having the steps belonging to $`E`$ in the unfavorable side. Upon defining $`G_k=_Eg_E`$ ($`G_k<2^k`$) one has

$`\begin{array}{c}𝒵(x=Nk,\{q_i\})=\left(2^NG_k\right)e^{\beta _{i=1}^Nq_i}+\hfill \\ +e^{\beta _{i=1}^Nq_i}{\displaystyle \underset{E}{}}g_Ee^{2\beta _{iE}q_i},\hfill \end{array}`$ (13)   
so that, by using the inequality $`\mathrm{ln}\overline{x}\overline{\mathrm{ln}x}`$ and averaging over the charge distribution, one obtains

$$f(Nk)f^{}\frac{1}{\beta N}\mathrm{ln}\left[1+\underset{E}{}g_E\frac{a(\mathrm{\Delta },q_o,\beta )^{|E|}1}{2^N}\right],$$

with $`a(\mathrm{\Delta },q_o,\beta )=\mathrm{exp}\left[2\mathrm{\Delta }^2\beta ^22\beta q_0\right]`$. This equation and its analogous in the $`q_0<0`$ case show that there is a delocalization temperature

$$\beta _{lower}=\frac{|q_0|}{\mathrm{\Delta }^2}$$
(14)   
such that, if $`\beta <\beta _{lower}`$, $`f(|Nk|)f^{}`$ and the chain delocalizes. This argument can be extended to the $`d`$-dimensional case, in which $`1G_k<(2d)^k`$, $`𝒵_d^{}(q_i)=(2d)^Ne^{\beta _{=1}^Nq_i}`$ and $`f_d^{}=\frac{1}{\beta }\mathrm{ln}2d|q_0|`$.

The bounds we have proved above allow to conclude that there is a critical value $`\beta _c`$ such that for values of $`\beta `$ smaller than $`\beta _c`$ the chain is delocalized in the favorable solvent, while for larger values it is adsorbed by the interface, with the estimates $`\beta _{lower}<\beta _c<\beta _{upper}`$ (it is easy to verify that $`\beta _{lower}<\beta _{upper}`$). The lower bound (14) and the upper bound (10), in the limit $`|q_0|/\mathrm{\Delta }1`$, show the same behavior found by using both an Imry-Ma type argument  and variational approaches .

Self-avoiding chain. All the results shown for a random chain can be readily generalized for a self-avoiding chain. Namely, a neutral chain is localized at all temperatures, whereas a non-neutral chain undergoes a localization transition at some critical temperature $`\beta _c`$.

The delocalization temperature $`\beta _{lower}`$ can be derived exactly in the same way, since the division of walks into classes according to the number of steps made in the unfavorable solvent does not depend on the self-avoidance constraint.

The upper bounds on the free energy, which allow to prove chain localization, requires instead some refinements with respect to the previous case. While the energy term is computed in the same way as before, the entropy term is different. Firstly, the connective constant ($`\kappa =2d`$ for a random walk in $`d`$ dimensions) is different. We recall that the existence of the connective constant, $`\kappa =lim_N\mathrm{}\mathrm{ln}S_N/N`$, for self-avoiding walks (SAW) has been rigorously established  ($`S_N`$ is the total number of $`N`$-steps SAW starting from the same site). The subleading correction of the form $`S_N\kappa ^NN^{\gamma 1}`$ is widely agreed upon, although not rigorously proved . Secondly we introduce the notion of loop, following e.g. , and consider only walks made up of $`N/k`$ blobs, each blob being a $`k`$-loop, in such a way that different blobs can be embedded independently, as well as for a random chain. A $`N`$-loop is a $`N`$-steps SAW, starting and ending on the interface, which always remains in the same half-space, with the further condition $`x_{01}x_{02}x_{i1}x_{i2}<x_{N1}x_{N2}i`$. It has been proved  that the free energy density of loops is the same as for SAW, $`\kappa _llim_N\mathrm{}\mathrm{ln}L_N/N=\kappa `$, where $`L_N`$ is the number of $`N`$-loops. The subleading correction is usually assumed in the same form as for the number of SAW:

$$L_N\kappa ^NN^{\gamma _s1}.$$
(15)   
These considerations are sufficient to generalize the previous results to the self-avoiding case, yielding the following bounds for the critical temperature:

$$\frac{\mathrm{ln}\kappa }{|q_0|G(\frac{\sqrt{2}|q_0|}{\mathrm{\Delta }})}\beta _c\frac{|q_0|}{\mathrm{\Delta }^2},$$
(16)   
which do not depend on the assumption (15) and is therefore rigorous. Again, in the limit $`|q_0|/\mathrm{\Delta }1`$ a better estimate $`\beta _{upper}`$ can be derived by using Eq. (15):

$$\beta _{upper}=\frac{1\gamma _s}{x_0^2G(x_0)}\mathrm{ln}\left(\sqrt{2}x_0\mathrm{\Delta }/|q_0|\right)\frac{|q_0|}{\mathrm{\Delta }^2}.$$
(17)   
Generic probability distribution. Up to now we have considered the hydrophobic charges as independently distributed Gaussian random variables. Actually, the results we have proved do not depend on this assumption. We will briefly sketch this in a few cases .

The argument showing localization at any temperature for a neutral chain holds true, both for random and self-avoiding chains, if $`\overline{\left|_{i=1}^kq_i\right|}\sqrt{k}`$ as $`k\mathrm{}`$. The central limit theorem ensures this for independent random variables having a generic probability distribution with finite variance and null mean. In the non-neutral case, the existence of a delocalization transition can be proved e.g. for a bimodal distribution. This corresponds to the more realistic case of two kinds of monomers, one hydrophilic and the other hydrophobic. We thus consider the generic bimodal distribution :

$$P\left(q_i\right)=\alpha \delta \left(q_iq_+\right)+\left(1\alpha \right)\delta \left(q_i+q_{}\right),$$
(18)   
with $`q_+,q_{}>0`$. The probability distribution (18) has three independent parameters, and fixing the average charge $`q_0=\alpha \left(q_++q_{}\right)q_{}`$ and the variance $`\mathrm{\Delta }=\sqrt{\alpha \left(1\alpha \right)}\left(q_++q_{}\right)`$ we are left with one free parameter. It is interesting to report the delocalization temperature $`\beta _{lower}`$, which provides a good estimate for the critical temperature in the previous cases:

$$\beta _{lower}^{bim}=\frac{\sqrt{\alpha \left(1\alpha \right)}}{2\mathrm{\Delta }}\left|\mathrm{ln}\left[1+\frac{q_0}{\sqrt{\alpha \left(1\alpha \right)}\mathrm{\Delta }\left(1\alpha \right)q_0}\right]\right|$$

Notice that in the limit of nearly neutral chain ($`|q_0|\mathrm{\Delta }`$) we get $`\beta _c^d\frac{|q_0|}{2\mathrm{\Delta }^2}`$, which is the same function of $`|q_0|`$ and $`\mathrm{\Delta }`$ as in the Gaussian case, suggesting the existence of a universal behavior. In the limit of nearly homogeneous chain ($`\mathrm{\Delta }|q_0|`$ which implies $`\alpha 0`$ or $`\alpha 1`$) instead $`\beta _{lower}^{bim}=\frac{1}{2\left(q_++q_{}\right)}\left|\mathrm{ln}\left[\frac{\alpha }{1\alpha }\frac{q_+}{q_{}}\right]\right|`$ diverges logarithmically in contrast with the Gaussian case.

We consider now the case in which the hydrophobic charges $`\left\{q_i\right\}`$ are not independent random variables, but are Gaussianly distributed with $`\overline{q_i}=q_0i`$, $`\overline{q_iq_j}\overline{q_i}\overline{q_j}=M_{ij}^1`$. We assume $`M_{ii}^1=\mathrm{\Delta }^2i`$, in analogy with the non-correlated case, and also translational invariance along the chain for the correlation matrix: $`M_{ij}=b(\left|ij\right|)`$. One can prove that if long range correlations decay exponentially or even algebraically the neutral chain is again localized at all temperatures. In fact, by assuming an algebraic decay, $`b\left(r\right)r^\eta `$, it turns out that $`\overline{\left|_{i=1}^kq_i\right|}k^{\delta /2}`$ with $`\delta =\mathrm{min}(\eta ,1)`$. Only if correlations are so strong that they do not vanish along the chain ($`\eta =0`$), the chain does not localize at all temperatures.

In the non neutral case the existence of the transition can be proved. For example the estimate of the delocalization temperature is

$$\beta _{lower}^{corr}=\underset{E}{\mathrm{min}}\left\{\frac{\left|E\right|\left|q_0\right|}{_{i,jE}M_{ij}^1}\right\}.$$
(19)   
If the charges are positively correlated ($`M_{ij}^1>0`$ for $`ij`$), chain localization is more favored than in the non-correlated case, whereas if charges are anti-correlated ($`M_{ij}^1<0`$ for $`ij`$) it is less favored.

Asymmetric interface potentials. Finally we extend our demonstrations to the random AB-copolymers studied by Sommer et al. . Their model corresponds to consider the following Hamiltonian:

$$=\underset{i}{}|q_i|[\lambda \theta (q_i)\theta (\stackrel{}{u}\stackrel{}{r}_i)+\theta (q_i)\theta (\stackrel{}{u}\stackrel{}{r}_i)],$$
(20)   
with the charges distributed according to Eq. (18) with $`\alpha =1/2`$ and $`q_+=q_{}`$ ($`|\lambda 1|`$ measures the potential asymmetry). Such an AB-copolymer (Eq. (20)) is equivalent to a non-neutral chain in symmetric potentials ($`\lambda =1`$), a case that we have already discussed. We have proved the existence of a delocalization transition for a neutral chain also in the Gaussian case. For both distributions, the delocalization temperature shows the behavior $`\beta _{lower}\frac{|\lambda 1|}{\mathrm{\Delta }}`$ in the limit of nearly symmetric potentials ($`\lambda 1`$), in agreement with the scaling law and the numerical results found in . On the contrary, in the highly asymmetric cases (small and large $`\lambda `$) different asymptotic behaviors for $`\beta _{lower}`$ occur .

To conclude, in this Letter we have proved several exact results on random heteropolymers in the presence of an interface. Namely, a neutral chain is localized at all temperatures, whereas a charged chain delocalizes at a finite temperature. The results are quite general and hold for ideal and self-avoiding chains, Gaussian and bimodal distribution with independent and correlated charges. Furthermore, our lower bounds for the transition temperature confirm previous estimates.

We would like to thank Jayanth Banavar, Cristian Micheletti and Flavio Seno for useful discussion and ongoing collaboration, and Enzo Orlandini for bringing references  to our attention.