Adsorption-induced conformational changes in protein diffusion-aggregation surface assemblies

Delphine Pellenc, Olivier Gallet, and Hugues Berry

Phys. Rev. E 72, 051904 – Published 2 November 2005

Abstract

Two-dimensional rigid colloid aggregation models may be applied to protein layers when no large conformational change is involved. Yet, following adsorption, several proteins undergo a conformational transition that may be involved in aggregative structures. Our focus here is how a conformational change might influence surface clustering in a diffusion-aggregation model. We propose a model including diffusion, aggregation, and unfolding of proteins that are randomly adsorbed onto a surface. Our model allows simulating the case where protein-protein interaction favors unfolding and the case where this interaction prevents it. We study the effect of a simple disk-to-rod unidirectional unfolding and investigate the morphology of the resulting clusters in the diffusion- and reaction-limited regimes. A rich variety of structures is produced, with fractal dimension differing from that in universal diffusive aggregation models. Increasing unfolding probability shifts the system from the neighbor-induced to the neighbor-prevented unfolding regime. The intermediate structures that arise from our model could be helpful in understanding the assembly of different observed protein structures.

Received 22 May 2005

DOI:https://doi.org/10.1103/PhysRevE.72.051904

Authors & Affiliations

Delphine Pellenc¹, Olivier Gallet¹, and Hugues Berry^1,2,*

¹ERRMECe, Universite de Cergy-Pontoise, 2 avenue Adolphe Chauvin, 95302 Pontoise Cedex, France
²Team Alchemy, INRIA Futurs, 4, rue Jacques Monod, 91893 Orsay Cedex, France

^*Corresponding author. Electronic address: hugues.berry@inria.fr

Article Text (Subscription Required)

Click to Expand

References (Subscription Required)

Click to Expand

Issue

Vol. 72, Iss. 5 — November 2005

Reuse & Permissions

Access Options

Author publication services for translation and copyediting assistance advertisement

Images

Figure 1
Depiction of the model. At each time step, proteins adsorb at a random position. They are then allowed to diffuse on the surface unless they unfold or aggregate. Neighbor-required unfolding $P_{I} = 0$ ; neighbor-prevented unfolding $P_{N} = 0$ ; neighbor-independent unfolding $P_{I} = P_{N}$ .Reuse & Permissions
Figure 2
Illustration of the cluster fractal dimension calculation using a box counting method. The fractal dimension $D_{f}$ is deduced from the slope of the log-log plot of the number of boxes versus the box dimension. Two unfolding probabilities are shown here, $P = 1$ (open symbols) and $10^{- 7}$ (filled symbols), in the case of neighbor-independent unfolding, i.e., $P_{N} = P_{I}$ . (a) Diffusion-limited regime, $P_{ag} = 1$ ; (b) reaction-limited regime, $P_{ag} = 10^{- 3}$ . For $P = 1$ a two-scale behavior is observed, so that each part of the curve is fitted independently and the two corresponding dimensions are indicated. In both panels, the curves have been shifted for clarity.Reuse & Permissions
Figure 3
Cluster fractal dimension $D_{f}$ versus the unfolding probability $P$ in the diffusion-limited regime where $P_{ag} = 1$ . (a) Neighbor-required unfolding, $P = P_{N}$ and $P_{I} = 0$ ; (b) neighbor-independent unfolding, $P = P_{N} = P_{I}$ ; and (c) neighbor-prevented unfolding, $P = P_{I}$ and $P_{N} = 0$ . The insets on top of each plot show examples of lattice configurations for each parameter set.Reuse & Permissions
Figure 4
Cluster fractal dimension $D_{f}$ versus the unfolding probability $P$ in the reaction-limited regime where $P_{ag} = 10^{- 3}$ . (a) Neighbor-required unfolding, $P = P_{N}$ and $P_{I} = 0$ ; (b) neighbor-independent unfolding, $P = P_{N} = P_{I}$ ; and (c) neighbor-prevented unfolding, $P = P_{I}$ and $P_{N} = 0$ . The insets on top of each plot show examples of lattice configurations for each parameter set.Reuse & Permissions
Figure 5
Unfolded protein fraction per cluster versus unfolding probability $P$ in the reaction- (continuous lines) and diffusion- (dotted lines) limited regimes for neighbor-prevented, -required, and -independent unfoldings. The symbols are the same as in Figs. 3, 4. All curves exhibit the same shape except in the neighbor-prevented regime ( $P = P_{I}$ ; $P_{N} = 0$ ; filled diamonds) where the unfolded fraction increases more slowly with $P$ in both regimes..Reuse & Permissions
Figure 6
Immunofluorescent staining of a fibronectin layer spontaneously formed upon adsorption onto (a), (b) hydroxyapatite or (c) cell culture glass. The cluster fractal dimension, estimated from a box counting method, is indicated at the bottom left of each picture. Each image is $300 \times 300 μ m$ .Reuse & Permissions

Physical Review E

covering statistical, nonlinear, biological, and soft matter physics