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Adsorption of Fibronectin, Fibrinogen, and Albumin on Tio2: Time-Resolved Kinetics, Structural Changes, and Competition Study

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Adsorption of Fibronectin, Fibrinogen, and Albumin on Tio2: Time-Resolved Kinetics, Structural Changes, and Competition Study Biointerphases (2012) 7:48 DOI 10.1007/s13758-012-0048-4 ARTICLE Adsorption of Fibronectin, Fibrinogen, and Albumin on TiO2: Time-Resolved Kinetics, Structural Changes, and Competition Study Marta Pegueroles • Chiara Tonda-Turo • Josep A. Planell • Francisco-Javier Gil • Conrado Aparicio Received: 19 June 2012 / Accepted: 18 July 2012 / Published online: 9 August 2012 Ó The Author(s) 2012. This article is published with open access at Springerlink.com Abstract An understanding of protein adsorption process fibronectin (Fn)]; and (b) the competition of those proteins is crucial for designing biomaterial surfaces. In this work, for adsorbing on TiO2 in a two-step experiment consisted with the use of a quartz-crystal microbalance with dissi- of sequentially exposing the surfaces to different mono- pation monitoring, we researched the following: (a) the protein solutions. Each protein showed a different process kinetics of adsorption on TiO2 surfaces of three extensively of adsorption and properties of the adlayer—calculated described proteins that are relevant for metallic implant using the Voigt model. The competition experiments integration [i.e., albumin (BSA), fibrinogen (Fbg), and showed that BSA displaced larger proteins such as Fn and Fbg when BSA was introduced as the second protein in the system, whereas the larger proteins laid on top of BSA M. Pegueroles Á C. Tonda-Turo Á J. A. Planell Á F.-J. Gil Á forming an adsorbed protein bi-layer when those were C. Aparicio introduced secondly in the system. Biomaterials, Biomechanics, and Tissue Engineering Group, Department of Material Science and Metallurgy, Technical University of Catalonia, Av. Diagonal 647, 08028 Barcelona, Spain 1 Introduction e-mail: [email protected] C. Tonda-Turo The first event taking place at the biomaterial-tissue e-mail: [email protected] interface is the interaction of water molecules and salt ions J. A. Planell with the surface of the implant. Shortly after the formation e-mail: [email protected]; [email protected] of the hydration layer, blood proteins start to crowd the F.-J. Gil biomaterial surface [1, 2]. Eventually, those proteins form a e-mail: [email protected] layer on top of the implanted material. When cells reach M. Pegueroles Á J. A. Planell Á F.-J. Gil the implant surface, they scan the layer of proteins looking Biomedical Research Networking Centre in Bioengineering, for activation factors to attach to that surface and react Biomaterials and Nanomedicine (CIBER-BBN), accordingly. Thus, protein adsorption on biomaterial sur- E50118 Zaragoza, Spain faces plays a crucial role in the integration of an implant in J. A. Planell the human body. Institute for Bioengineering of Catalonia (IBEC), Ideally, the surface properties of the implantable mate- Baldiri Reixac 13, 08028 Barcelona, Spain rial will trigger appropriate responses for specific applica- tions by controlling the type, amount, and conformation of Present Address: C. Aparicio (&) the proteins that will adsorb on the implant. Understanding Department of Restorative Sciences, School of Dentistry, the process of protein adsorption is then crucial to the Minnesota Dental Research Center for Biomaterials and surface design of biomaterials. Biomechanics (MDRCBB), University of Minnesota, Proteins are a special, highly complex, and important 16-212 Moos Tower, 515 Delaware St. S.E, Minneapolis, MN 55455, USA case of particles adsorbing at surfaces. Protein adsorption is e-mail: [email protected] a dynamic process involving non-covalent interactions 123 Page 2 of 13 Biointerphases (2012) 7:48 such as hydrophobic interactions, electrostatic forces, between different studies as a consequence of the different hydrogen bonding and van der Waals’ forces [3]. On the experimental conditions. However, some general charac- one side, the non-covalent interactions are controlled by teristics of protein interaction with titanium surfaces can be multiple protein parameters, such as protein size, pI, sec- found. Proteins in solution accumulate spontaneously at ondary and tertiary structure [4, 5]. On the other side, materials interfaces and, in the case of titanium surfaces, surface properties such as surface energy, roughness and most of them adsorb irreversibly since the process is highly chemistry have been also identified as key factors influ- energetically favorable [26]. However, some adsorbed encing the process of protein adsorption [4, 6–8]. proteins can detach due to protein competition and dis- Protein adsorption to surfaces is the first step in many placement processes [26]. The replacement of initially fundamental biological processes such as blood coagula- adsorbed proteins with high mobility by new proteins with tion cascade and trans-membrane signalling [4]. There are lower mobility but higher affinity for the surface is the so- multiple proteins in human blood plasma. Among them, called Vroman effect [4]. Different adsorption isotherms fibrinogen (Fbg), fibronectin (Fn) and albumin (Alb) which reported in the literature [1, 27, 28] showed high affinity of constitute a set of well-known, thoroughly characterized, fibronectin to titanium surfaces. extensively described proteins [9]. Several studies have Proteins systems are very complex and thus, measure- suggested that platelet adhesion and activation might be ments with well-defined model systems carried out under particularly affected by adsorbed fibrinogen, a mediator of well-controlled conditions are essential to understand the platelet activation via its direct interaction with platelet underlying mechanisms of protein adsorption [29]. Dif- receptors [10–12]. Fibronectin is a key component of the ferent techniques have been used for quantitatively char- extracellular matrix (ECM), is a large dimeric glycoprotein acterize protein adsorption on solid surfaces. Most of them triggering cell adhesion [13], undergoes cell-driven either (a) rely on labelling adsorbing molecules with a assembly in supramolecular fibrils, and provides specific radioactive or fluorescent tag and comparing their signal on binding sites for various ECM biopolymers [14]. Albumin the surface before and after adsorption or (b) are based in is the most abundant component of many biofluids, serving changes in the optical properties of the surface while the as transport media for various metabolites and as regulator layer of proteins is being adsorbed, such as ellipsometry of osmotic pressure [14, 15]. Moreover, albumin is a and surface plasmon resonance. The former are laborious widespread protein used to block ‘non-specific’ cell adhe- procedures that do not allow real-time monitoring of the sion [16], but some controversy exists given that albumin studied process. The later provides us with real-time data has been found to promote platelet and macrophage of the formation of the protein layer; however, information adhesion [17, 18]. of the structural/conformational changes of the protein Metal surfaces are, with few exceptions, covered with a layer is not obtained. We used a quartz-crystal microbal- metallic oxide layer of a few to several nanometers in ance with dissipation monitoring (QCM-D). With QCM-D thickness. As a consequence, interactions between metal the kinetics of both mass changes and structural/mechani- implants, proteins, and cells are governed by the physical– cal properties changes are obtained [30–32]. This is pos- chemical properties of their corresponding metallic oxides. sible because the equipment simultaneously collects both The excellent chemical inertness, corrosion resistance, re- the resonant frequency and the energy dissipation signals passivation ability, and biocompatibility of titanium are of a quartz crystal sensor coated with the material in thought to result from the chemical stability (high corro- question. The change in mass of the sensor while the sion resistance) a thermodynamically stable state and proteins adsorb produces changes in the frequency of the structure of the titanium oxide film mainly composed of sensor. Also, the structural and conformational effects at TiO2 at physiological pH values [19–22]. The following the protein layer when water incorporates into and interacts crystal structures have been recognized for TiO2: rutile with the protein layer can be monitored by tracking chan- (tetragonal), anatase (tetragonal), and brookite (ortho- ges in the energy dissipation of the system [33]. However, rhombic). TiO2 also exists in an amorphous state [23]. the specific structural changes have to be further investi- Regarding the surface oxide layer on c.p. Ti dental implant gated with complementary experimental techniques. systems, spectroscopic studies suggest that the oxide is Even though increasing number of studies have inves- amorphous and its thickness is approximately 2–17 nm tigated the process of protein adsorption on biomaterials [22–24]. there is still lack of fundamental knowledge on how some In vitro studies have shown that material surface prop- specific combinations of relevant proteins interact with erties, including the negatively charged and hydrophilic synthetic substrates of clinical interest. We report here on TiO2 layer, are of importance for protein adsorption [25]. (a) the kinetics of the protein adsorption process, (i.e. One reported issue is that in vitro adsorption of the same evolution of mass and structure of the protein layer on protein on the same type of surface may vary considerably sensors coated with TiO2 from three different monoprotein 123 Biointerphases (2012)
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