Effects of Macromolecular Crowding on the Collapse of Biopolymers

Abstract

Experiments show that macromolecular crowding modestly reduces the size of intrinsically disordered proteins (IDPs) even at volume fraction (φ) similar to that in the cytosol whereas DNA undergoes a coil-to-globule transition at very small φ. We show using a combination of scaling arguments and simulations that the polymer size Rg(φ) depends on x = Rg(0)/D where D is the φ-dependent distance between the crowders. If x < ∼ O(1), there is only a small decrease in Rg(φ) as φ increases. When x O(1), a cooperative coil-to-globule transition is induced. Our theory quantitatively explains a number of experiments.The importance of crowding in biology is being increasingly appreciated because of the realization that cellular processes occur in a dense medium containing polydisperse mixture of macromolecules. A number of studies have been performed to understand the role crowding particles play in inducing structural transitions in disordered chiral homopolymers [1,2], in protein [3][4][5] and RNA folding [6][7][8], gene regulation through DNA looping [9], genome compaction [10]. Some of the consequences of crowding can be qualitatively explained using depletion interaction introduced by Asakura and Oosawa (AO) [11]. In the AO picture, the crowding particles, treated as hard objects, vacate the interstitial space in the interior of the macromolecule to maximize their entropy. As a result, an osmotic pressure due to crowders reduces the size of the macromolecule.The predictions based on the AO theory rationalize the impact of crowding effects on synthetic and biological polymers qualitatively provided only excluded volume interactions between the crowding particles and the macromolecules dominate. Even in this limit two questions of particular importance for experiments on biopolymers require scrutiny. (i) What is the extent of crowding-induced compaction in finite-sized polymer coils? These systems are minimal models for unfolded and intrinsically disordered proteins (IDPs), and in some limits (random loop model) also provide a useful caricature of chromosome folding. (ii) For polymers with N monomers, what is the dependence of the average radius of gyration, R g (φ) (≡ R 2 g (φ)1/2 ), as a function of the volume fraction φ and size of the crowders? It is important to answer these questions quantitatively to resolve seemingly contradictory conclusions reached in recent experiments.Here, we answer these questions using a combination of scaling arguments and computer simulations. The two length scales that determine the degree of polymer compaction in solution, with crowding particles interacting with each other and the polymer via hard repulsions, are R g (0) (the size of the coil at φ = 0), and the average distance D between the crowders. We propose a scaling relation to predict the dependence of R g (φ) on φ based on the expectation that when D < ∼ R g (0) the osmotic pressure acting on the polymeric chain should reduce the polymer size. If correlations between the crowding particles are negligible, as explicitly shown h...

Equilibrium simulation of trp-cage in the presence of protein crowders

“…[32][33][34][35][36][37][38] In many cases, the crowders have been modeled as hard spheres. To enable more detailed simulations, a post-processing alternative to direct simulation has been developed.…”

D meson production in heavy ion collisions with CMS

“…The R AA of inclusive charged particles are superimposed for equivalent event selections [8]. Experimental results are compared to various theoretical calculations [9][10][11][12][13][14][15][16][17].…”

Production of non-photonic electrons in U+U collisions at √sNN= 193 GeV at the STAR experiment

“…The nuclear modification factor of NPE Figure 4: Left: Nuclear modification factor of NPE versus p T in U+U collisions compared to AuAu collisions and model [19], [20], [21]. Right: Nuclear modification factor of NPE in U+U and Au+Au collisions, D mesons in U+U and Au+Au collisions [4] and π ± in Au+Au collisions [22] versus number of participants.…”

“…R AA of NPE in U+U collisions is compared to theoretical model including CNM effects (Cronin effect and initial state energy loss), QGP effects such as jet quenching, and new attenuation mechanism for open heavy flavor mesons, called collisional dissociation, originating from short formation times of D and B mesons. The dashed green line represents the case with lower initial state energy loss but large Cronin effect and the dot-dashed magenta line the case with higher initial state energy loss and small Cronin effect [19], [20], [21]. In addition, nuclear modification factor of NPE as a function of number of participants is plotted in Fig.…”