Adsorption of human serum albumin on the chrysotile surface: a molecular dynamics and spectroscopic investigation

Abstract

The human serum albumin (HSA) secondary structure modifications induced by the chrysotile surface have been investigated via computational molecular dynamics (MD) and experimental infrared spectroscopy (FTIR) on synthetic chrysotile nanocrystals coated with different amount of HSA. MD simulations, conducted by placing various albumin subdomains close to the fixed chrysotile surface, show an initial adsorption phase, accompanied by local rearrangements of the albumin motifs in contact with the chrysotile layer. Next, large-scale rearrangements follow with consequent secondary structure modifications.Gaussian curve fitting of the FTIR spectra obtained for HSA-coated synthetic chrysotile nanocrystals has allowed the quantification of HSA structural modifications as a function of the amount of protein adsorbed. The experimental results support the atomistic computer simulations providing a realistic description of the adsorption of plasma proteins onto chrysotile and unravelling a key step in the understanding of asbestos toxicity.

Molecular modelling of protein adsorption on the surface of titanium dioxide polymorphs

“…After that, a steered MD simulation was carried out assuming a pulling force acting on the fibronectin module to mimic the desorption experimentally induced by an atomic force microscope tip. Finally, another paper reported MD simulations of the adsorption of the same albumin subdomain considered by us on a silicate surface of chrysotile, Mg 3 Si 2 O 5 (OH) 4 [16]. Adopting an implicit solvent, the albumin subdomain was found to better interact with this polar, hydrophilic surface through its polar sides, but eventually to show a very large spreading to almost a single monolayer of amino acids.…”

“…However, other groups have independently chosen a somewhat similar strategy [12], or have explicitly adopted our procedure [16]. Our simulation protocol basically involves two steps: (i) first, we minimize the energy of the system using different initial orientations of the protein close to the surface, using an implicit solvent through an effective distance-dependent dielectric constant and (ii) then we perform MD runs in the implicit solvent at 300 K for selected arrangements, considering both the lowest and the highest energy minimum obtained in the initial minimizations to follow the surface rearrangements on a bare surface.…”

“…For instance, in our group, we considered the adsorption of unlike protein subdomains and of lysozyme on hydrophobic graphite and on the amorphous surface of a hydrophilic polymer, together with sequential adsorption on graphite [4][5][6][7][8][9][10]. With similar methods, other groups considered different ceramic surfaces, such as titanium dioxide (TiO 2 ) (rutile) [11], MgO [12], SiO 2 (assumed to mimic atomically flat mica) [13,14], hydroxyapatite, the mineral component of bones [15], or a silicate surface of chrysotile [16], but self-assembled monolayers were also modelled [17]. Some of these papers were already reviewed in earlier studies [10,18], and shall be briefly commented upon later.…”

Disentangling protein–silica interactions

“…The total electrostatic charge of pepsin, −6|e|, was determined previously by calculating the pKa of the protein side chains at pH = 3.6 [26], where the protein loading in SBA-15 is maximal. In particular, His53, Lys319, Arg307 and Arg315 were modelled as positively charged residues, whereas 10 Asp residues (11,87,118,138,171,195,215,242,290,314) were unprotonated (negatively charged). Two model silica surfaces were investigated, one electrically neutral, and one with surface charge of −4|e| (figure 1).…”

“…Actually, the investigation of protein-solid surfaces interactions via simulations, in spite of being still in its pioneering phases, has been of great help in unravelling many aspects of the general problem [8], especially concerning interactions with flat surfaces. For instance, lysozyme on hydrophylic silica and graphite surfaces [9,10], and albumin subdomains on chrysotile and graphite [11,12] were investigated, evidencing conformational alterations and/or partial unfolding of the protein upon adhesion. Owing to the interest in the field, a growing number of simulation studies about the surface adsorption of proteins has been performed in the last few years [13,14].…”