An Equilibrium Model for the Combined Effect of Macromolecular Crowding and Surface Adsorption on the Formation of Linear Protein Fibrils  Travis Hoppe, Allen P. Minton  Biophysical Journal  Volume 108, Issue 4, Pages 957-966 (February 2015) DOI: 10.1016/j.bpj.2014.12.033 Copyright © 2015 Biophysical Society Terms and Conditions

Figure 1 Principal states of the model system. Tracer species are depicted as red circles and spherocylinders, and crowder species are shown as gray circles. Upper left: tracer monomer in bulk; upper right: tracer n-mer in bulk; lower left, tracer monomer in the surface compartment; lower right: tracer n-mer in the surface compartment. To see this figure in color, go online. Biophysical Journal 2015 108, 957-966DOI: (10.1016/j.bpj.2014.12.033) Copyright © 2015 Biophysical Society Terms and Conditions

Figure 2 Regions shaded with wavy lines indicate the volumes excluded by a spherocylindrical tracer n-mer to a spherical crowder particle in the bulk (top) and when adsorbed to the surface (bottom). The region shaded with dots in the lower image indicates the volume excluded by the hard wall to a crowder sphere in the absence of adsorbed tracer n-mer. To see this figure in color, go online. Biophysical Journal 2015 108, 957-966DOI: (10.1016/j.bpj.2014.12.033) Copyright © 2015 Biophysical Society Terms and Conditions

Figure 3 MC calculation of the logarithm of the ratio of successful insertion probabilities of an n-mer in the bulk to that at the surface, plotted for monomers (black circles), dimers (magenta squares), trimers (blue diamonds), and tetramers (red triangles) as a function of the fraction of volume occupied by crowder. Symbols indicate calculated results, and dashed curves are empirical quadratic functions to guide the eye. To see this figure in color, go online. Biophysical Journal 2015 108, 957-966DOI: (10.1016/j.bpj.2014.12.033) Copyright © 2015 Biophysical Society Terms and Conditions

Figure 4 Dependence of RV on ϕ, calculated according to Eq. 19. Symbols correspond to results obtained from insertion probabilities of monomer (black circles), dimer (magenta squares), trimer (blue diamonds), and tetramer (red triangles). The calculated points are empirically described by the straight line calculated using values of the intercept and slope given in the text. To see this figure in color, go online. Biophysical Journal 2015 108, 957-966DOI: (10.1016/j.bpj.2014.12.033) Copyright © 2015 Biophysical Society Terms and Conditions

Figure 5 Dependence of ln(fb,n+1/fb,n)∗ (dashed curves) and ln(fs,n+1/fs,n) (solid curves) on ϕ, calculated for ΔHads = −.5, lnctot∗0 = 0 (red circles) and ΔHads = 0, lnctot∗0 = −.5 (black squares). To see this figure in color, go online. Biophysical Journal 2015 108, 957-966DOI: (10.1016/j.bpj.2014.12.033) Copyright © 2015 Biophysical Society Terms and Conditions

Figure 6 Dependence of ϕcrit on ΔHads calculated for lnctot∗0 = −0.5 (solid curve) and 0 (dashed curve). Biophysical Journal 2015 108, 957-966DOI: (10.1016/j.bpj.2014.12.033) Copyright © 2015 Biophysical Society Terms and Conditions

Figure 7 Equilibrium properties of the model calculated for nmax = 800, plotted as functions of ϕ. Vertical dotted lines indicate values of ϕcrit calculated for the corresponding value of ΔHads. (A) Average size of bulk oligomers. (B) Average size of adsorbed oligomers. (C) Fraction of tracer adsorbed calculated for fsurface = 0.001. (D) Fraction of tracer adsorbed calculated for fsurface = 0.1. Multiple curves plotted in panels B–D correspond to results obtained for ΔHads = −0.2 (left), 0 (center), and 0.2 (right), respectively. Biophysical Journal 2015 108, 957-966DOI: (10.1016/j.bpj.2014.12.033) Copyright © 2015 Biophysical Society Terms and Conditions

Figure 8 Equilibrium properties of model calculated for nmax = 800, plotted as functions of ΔHads for ϕ = 0.18. Vertical dotted lines indicate the value of ΔHads,crit for this value of ϕ. (A) Average size of adsorbed oligomers. (B) Fraction of tracer adsorbed, calculated for fsurface = 0.001 (solid curve) and fsurface = 0.1 (dashed curve). Biophysical Journal 2015 108, 957-966DOI: (10.1016/j.bpj.2014.12.033) Copyright © 2015 Biophysical Society Terms and Conditions