Nanoparticles (NPs) are increasingly used to target bacteria as an alternative to antibiotics. Nanotechnology may be particularly advantageous in treating bacterial infections. Examples include the utilization of NPs in antibacterial coatings for implantable devices and medicinal materials to prevent infection and promote wound healing, in antibiotic delivery systems to treat disease, in bacterial detection systems to generate microbial diagnostics, and in antibacterial vaccines to control bacterial infections. The antibacterial mechanisms of NPs are poorly understood, but the currently accepted mechanisms include oxidative stress induction, metal ion release, and non-oxidative mechanisms. The multiple simultaneous mechanisms of action against microbes would require multiple simultaneous gene mutations in the same bacterial cell for antibacterial resistance to develop; therefore, it is difficult for bacterial cells to become resistant to NPs. In this review, we discuss the antibacterial mechanisms of NPs against bacteria and the factors that are involved. The limitations of current research are also discussed.

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The antimicrobial activity of nanoparticles: present situation and prospects for the future

An appropriate cellular response to implanted surfaces is essential for tissue regeneration and integration. It is well described that implanted materials are immediately coated with proteins from blood and interstitial fluids, and it is through this adsorbed layer that cells sense foreign surfaces. Hence, it is the adsorbed proteins, rather than the surface itself, to which cells initially respond. Diverse studies using a range of materials have demonstrated the pivotal role of extracellular adhesion proteins--fibronectin and vitronectin in particular--in cell adhesion, morphology, and migration. These events underlie the subsequent responses required for tissue repair, with the nature of cell surface interactions contributing to survival, growth, and differentiation. The pattern in which adhesion proteins and other bioactive molecules adsorb thus elicits cellular reactions specific to the underlying physicochemical properties of the material. Accordingly, in vitro studies generally demonstrate favorable cell responses to charged, hydrophilic surfaces, corresponding to superior adsorption and bioactivity of adhesion proteins. This review illustrates the mediation of cell responses to biomaterials by adsorbed proteins, in the context of osteoblasts and selected materials used in orthopedic implants and bone tissue engineering. It is recognized, however, that the periimplant environment in vivo will differ substantially from the cell-biomaterial interface in vitro. Hence, one of the key issues yet to be resolved is that of the interface composition actually encountered by osteoblasts within the sequence of inflammation and bone regeneration.

Mediation of Biomaterial–Cell Interactions by Adsorbed Proteins: A Review

https://www.zora.uzh.ch/id/eprint/44154/1/Rabe1.pdf

Understanding protein adsorption phenomena at solid surfaces

Organic polyelectrolytes in water treatment.

Integrin-mediated cell adhesion to proteins adsorbed onto synthetic surfaces anchors cells and triggers signals that direct cell function. In the case of fibronectin (Fn), adsorption onto substrates of varying properties alters its conformation/structure and its ability to support cell adhesion. In the present study, self-assembled monolayers (SAMs) of alkanethiols on gold were used as model surfaces to investigate the effects of surface chemistry on Fn adsorption, integrin binding, and cell adhesion. SAMs presenting terminal CH(3), OH, COOH, and NH(2) functionalities modulated adsorbed Fn conformation as determined through differences in the binding affinities of monoclonal antibodies raised against the central cell-binding domain (OH > COOH = NH(2) > CH(3)). Binding of alpha(5)beta(1) integrin to adsorbed Fn was controlled by SAM surface chemistry in a manner consistent with antibody binding (OH > COOH = NH(2) > CH(3)), whereas alpha(V) integrin binding followed the trend: COOH >> OH = NH(2) = CH(3), demonstrating alpha(5)beta(1) integrin specificity for Fn adsorbed onto the NH(2) and OH SAMs. Cell adhesion strength to Fn-coated SAMs correlated with alpha(5)beta(1) integrin binding (OH > COOH = NH(2) > CH(3)), and experiments with function-perturbing antibodies demonstrated that this receptor provides the dominant adhesion mechanism in this cell model. This work establishes an experimental framework to analyze adhesive mechanisms controlling cell-surface interactions and provides a general strategy of surface-directed control of adsorbed protein activity to manipulate cell function in biomaterial and biotechnological applications.

Surface chemistry modulates fibronectin conformation and directs integrin binding and specificity to control cell adhesion

This work compares the spreading and relaxation rates of albumin and fibrinogen, inferred from single-component and competitive adsorption kinetic experiments, on model surfaces of varying hydrophobicity. Kinetics from the single-component studies revealed a constant spreading rate, where the adsorbed protein footprint grew linearly in time for at least 15 min. This spreading rate increased with substrate hydrophobicity (ranging from 0.02 to 0.16 nm2/molecule/s for albumin and from 0.04 to 0.26 nm2/molecule/s for fibrinogen), resulting in a larger extent of footprint growth and a lower ultimate coverage on hydrophobic surfaces when compared with hydrophilic surfaces at the same adsorption conditions. Competitive adsorption studies were in qualitative agreement with the single-component experiments but were able to probe longer spreading time scales. Although spreading appeared to occur initially at a constant rate in the competitive experiments, after 2 h the spreading rate had slowed dramatically and the...

Effect of Surface Hydrophobicity on Adsorption and Relaxation Kinetics of Albumin and Fibrinogen: Single-Species and Competitive Behavior

We report the kinetic behavior of albumin and fibrinogen adsorption and relaxation from gentle shearing flow and phosphate buffer onto C16 self-assembled monolayers. The adsorption kinetics were generally transport-limited; however, the ultimate coverages depended on the rates at which protein molecules arrived at the surface, suggesting that interfacial relaxations determined the ultimate coverage. Of particular note was a dependence of the ultimate coverage of both proteins on the wall shear rate, in addition to the influence of the bulk solution concentration. Analysis of single protein experiments revealed interfacial protein relaxation rates of 0.12 and 0.15 nm2 molecule-1 s-1 for albumin and fibrinogen, respectively. These rates were constant over the range of experimental conditions and represent the initial relaxation rates after protein adhesion to the surface. The initial protein footprints were consistent with the free solution protein dimensions and, in the case of albumin, grew over a factor ...

Adsorption and Relaxation Kinetics of Albumin and Fibrinogen on Hydrophobic Surfaces: Single-Species and Competitive Behavior

Using total internal reflectance fluorescence (TIRF), we observe that lysozyme adsorption onto hydrophobic surfaces can exhibit kinetic overshoots at some conditions, while, at lower free solution concentrations or flow rates over the surface, the coverage monotonically approaches its final value. This behavior is explained by an interfacial relaxation from an end-on to a side-on orientation, which occurs by rollover and not by the displacement of end-on adsorbed proteins by side-on adsorbing proteins. Rollover and displacement models are compared with data to prove this point. Ultimately, we quantitatively predict the kinetic traces for a variety of different adsorption histories (free solution concentration, flow rate, interruption of adsorption by flowing solvent) using a rollover model with reversible transport-limited adsorption of end-on oriented lysozyme and a single rollover rate constant.

Adsorption and reorientation kinetics of lysozyme on hydrophobic surfaces

This work examined the relationship between footprint growth and adsorption energetics for fibrinogen on model hydrophobic and hydrophilic surfaces. For adsorption runs at different free solution concentrations and flow rates in a slit-shear flow cell, single surface-dependent relaxation times were found on each of two model surfaces. By use of each relaxation time in an exponential growth model, predictions of the footprint size distributions were made for different adsorption histories. Then, from desorption rate measurements and a reversible binding model, the sizes of loosely and tightly bound populations were determined, in addition to the binding energy of the loosely bound population. These binding energies were then compared with the footprint size distributions to reveal markedly different behavior on the hydrophobic and hydrophilic surfaces. On the hydrophobic surface, a single footprint size correlated with a binding energy of 6kT, a feature that was independent of adsorption history and the fo...

Fibrinogen Adsorption on Hydrophilic and Hydrophobic Surfaces: Geometrical and Energetic Aspects of Interfacial Relaxations

Using AFM (atomic force microscopy) to probe protein conformation and arrangement, and TIRF (total internal reflectance fluorescence) to monitor kinetics, fibrinogen adsorption on three different silica-based surfaces was studied:  the native oxide on silicon, acid-etched microscope slides, and acid-etched polished glass. The three are chemically similar, but the microscope slide is rougher and induces AFM tip instabilities that appear as high spots on the bare surface. Fibrinogen's conformation and transport-limited adsorption kinetics are found to be quantitatively similar on all three surfaces. Further, the number of adsorbed proteins in progressive AFM micrographs quantitatively match the coverages measured by TIRF during early adsorption. Surfaces appear full, via AFM, when adsorbed amounts are about an order of magnitude below their true saturation levels (via TIRF) because, above about 0.26 mg/m2, individual proteins cannot be discerned. The results demonstrate how the appearance of AFM micrographs...

Maria M. Santore

Papers

Effect of Surface Hydrophobicity on Adsorption and Relaxation Kinetics of Albumin and Fibrinogen: Single-Species and Competitive Behavior

Adsorption and Relaxation Kinetics of Albumin and Fibrinogen on Hydrophobic Surfaces: Single-Species and Competitive Behavior

Adsorption and reorientation kinetics of lysozyme on hydrophobic surfaces

Fibrinogen Adsorption on Hydrophilic and Hydrophobic Surfaces: Geometrical and Energetic Aspects of Interfacial Relaxations

Fibrinogen adsorption on three silica-based surfaces: conformation and kinetics.