Professor of Chemical Engineering
Ph.D. 1993, University of Minnesota
Phone: 1 (203) 432-7983
Fax: 1 (203) 432-4387
Office: Mason Laboratory 304
Research Summary

The engineering of materials containing biological structure offers the promise of new devices and processes of great potential impact on the quality of human life. Research efforts in the Van Tassel group focus on understanding, predicting, and controlling the incorporation of biomolecular or biomimetic entities onto or within synthetic materials. Principal focus areas include biomolecules at interfaces and templated materials, and a balanced blend of theory, computer simulation, and experiment are employed. Below are synopses of several recent and ongoing projects and a list of publications.

Protein adsorption kinetic modeling

The behavior of biomolecules at the solid-liquid interface is crucial to technologies involving molecular surface placement, yet is poorly understood [1]. In particular, theoretical prediction of the temporal evolution of an adsorbed protein layer remains an unsolved problem. Key challenges include identification of relevant (often irreversible) adsorption mechanisms, construction of a suitably coarse-grained model description, and theoretical approximation of adsorbed layer structural properties. We are developing a mesoscopic description accounting for the influence of protein-protein interactions on surface attachment and surface-induced conformational change [2-7]. We find both optical waveguide lightmode spectroscopy (OWLS) experiments and scaled particle theoretical methods (SPT) to be extremely useful here. Using SPT, we accurately and efficiently calculate the interfacial cavity function, an important structural metric influencing the rates of adsorption and subsequent transitions [4]. Using OWLS to measure detailed adsorption/desorption kinetics of several representative proteins, we isolate transport and surface limited adsorption regimes. These findings suggest coupling a boundary layer “transport” description to the SPT “surface” model; the resultant generalized description enables accurate prediction for several protein-surface systems over a broad coverage range [6].

Protein adsorption kinetic modeling

Protein adsorption kinetics as measure of adlayer structure and history dependence

Protein adsorption is often strongly history dependent owing to the slow relaxation of non-equilibrium structures. The rate at which molecules adsorb is exquisitely sensitive to, and thus a sensitive measure of, interfacial structure; adsorption kinetics may therefore serve both to identify and quantify history dependence. We are using optical waveguide lightmode spectroscopy (OWLS) in multi-step mode [8-10] – where an adsorbing surface is alternately exposed to a protein solution and one free of protein – as well as complementary theoretical methods [11, 12], to compare adsorption rates onto interfacial layers of identical composition but different formation histories. Contributions to the overall kinetics from the adsorption/desorption rate constants and the interfacial one-body cavity function (a measure of the probability of a “cavity” on the surface free of protein) may be isolated from OWLS kinetic data. An important discovery is the increased rate of adsorption (and increased value of the cavity function) for many protein-surface systems from a first to a subsequent adsorption step, suggesting a surface-induced clustering transition. We are also extending this treatment to quantify the degree of specific and non-specific antibody attachment to adsorbed protein layers [13]. We envision these methods to lead to more accurate antibody-based biosensing and biomaterial-host interaction analysis.

Protein adsorption kinetics as measure of adlayer structure and history dependence

Adsorbed protein conformational transition by Monte Carlo simulation

Proteins often undergo changes in internal conformation upon adsorbing to a surface. These transitions have important implications to protein structure and function, yet fundamental questions remain open, e.g. When do transitions involve an activation barrier? What role does surface hydrophobicity / hydrophilicity play? How do transition length and time scales depend upon intra-protein and protein-surface interactions? We are addressing these questions by investigating the conformational thermodynamics of an adsorbed lattice model protein [14, 15]. Using multicanonical Monte Carlo simulation methods, we obtain the complete density of states, and thus also the entropy and free energy profiles linking native to conformationally altered proteins. Interesting findings include i) the sensitivity of the free energy profile to surface type (i.e. hydrophobic / hydrophilic) and ii) the presence of activation free energy barriers for all but the strongest adsorbing surfaces. In addition to answering fundamental questions on the nature of the surface-induced conformational transition, these results facilitate our inclusion of this important feature within mesoscopic models of adsorption kinetics.

Adsorbed protein conformational transition by Monte Carlo simulation

Substrate electric potential control of protein/polyelectrolyte adsorption

Owing to the presence of pH-dependent charges, the adsorption of protein and charged polymer may be controlled through the substrate electric potential. We envision creating highly spatially and/or orientationally ordered layers through electric potential control. Toward this end, our initial goal is to understand the influence of substrate potential on the adsorption process. We have modified optical waveguide lightmode spectroscopy (OWLS) to allow for in situ measurement of macromolecular adsorption kinetics under an applied voltage [16]. We find the application of a modest anodic potential (ca. 1 V) to result in significantly enhanced adsorption of certain protein [17, 18] and polyelectrolyte [19, 20] species. The common feature of these systems is the presence of weakly basic sites, and we attribute the enhanced adsorption to slow conformational changes associated with breaking the surface contacts of these sites. We are also extending this work to layer-by-layer films – formed by the alternate addition of oppositely charged species – and find the enhanced adsorption of the first layer under an applied potential to lead to a significantly enhanced multilayer film growth [19]. We are currently working to exploit this effect to create tailored polymer/protein films for biosensing and tissue engineering applications.

Substrate electric potential control of protein/polyelectrolyte adsorption

Protein/polyelectrolyte multilayer assemblies as biomaterial coatings

Fibronectin (Fn) is a matrix protein known to induce cell adhesion and spreading through its cell-binding site. Biomaterials coated with Fn are excellent candidates for tissue engineering applications. One of our interests is to optimize the available fraction of Fn binding sites. In collaboration with Howard Matthew, we are investigating the attachment of Fn via an immobilized ligand specific to a region away from the cell-binding site, so as to promote an orientation favoring cell-binding site exposure [21]. The results are striking: we find human umbilical endothelial calls to spread to a significantly greater extent on orientated fibronectin. Another interest concerns layer-by-layer polyelectrolyte nanofilms. This new biomaterial coating method has shown great promise, but the influence of a Fn terminal layer on cell response is largely unknown. In collaboration with Mark Saltzman and Guangzhao Mao, we find multilayer charge and hydration degree to greatly influence Fn terminal layer properties [22], and for cells to spread more evenly on positively charged / poorly hydrated films [23]. These studies illustrate the potential of Fn terminated multilayer assemblies as biomaterial coatings.

Protein/polyelectrolyte multilayer assemblies as biomaterial coatings

Adsorption in a templated porous material

Molecular templating is a promising means to incorporate complementary shape or biomimetic structure within a synthetic material, but is poorly understood on a fundamental level. One of our goals is to establish a theoretical framework for modeling adsorption in templated materials. Our model material – as inspired by the actual formation process – is a quenched, equilibrated matrix/template molecular configuration with the template component removed [24-26]. This model meets the challenges of i) representing the material in a simple yet realistic way, ii) capturing the essential features of the templating process, and iii) being amenable to theoretical treatment. We apply the replica method in order to treat the problem using standard liquid-state integral equation theories and investigate the influence of template size, shape, and density on the adsorptive properties of these non-equilibrium materials [27-30]. We find the adsorption isotherm and the phase envelope to depend sensitively on template size and density; these results illustrate the impressive degree of control over a porous material’s adsorptive properties available through templating strategies.

Adsorption in a templated porous material

Templated molecular recognition materials

Molecular recognition refers to the strong and highly specific binding between complementary patterns of weakly interacting sites. Although more common in biology, synthetic materials may also exhibit highly selective binding, as e.g. when formation occurs in the presence of a template species. Progress in “templated molecular recognition” (TMR) is currently limited, however, by our poor fundamental understanding of the templating process and its influence on material structure and recognition ability. One of our key objectives is to develop a theoretical description of TMR. We take a molecular approach, inspired by the material formation process, and employ a replica Ornstein-Zernike method to calculate the thermodynamic properties of systems composed of interacting sites [31]. An important finding is the selectivity factor of systems composed of hard sphere clusters – as determined by the ratio of activities of species identical to, and structurally different from, the template species – exceeding that of a non-selective material by up to an order of magnitude. These methods are enabling us to rationally design TMR materials for biosensing and tissue engineering applications.

Templated molecular recognition materials

Macro-ion influence on colloidal force

Surface forces between small “colloidal” objects (particles, proteins, cells) govern many industrially and medically important systems. An important contribution to the overall force is the depletion interaction, brought about by an added component whose size is larger than the (usually water) solvent but smaller than the colloidal objects themselves (see figure). A net force results from the unbalanced osmotic pressure, in the region near contact between two larger objects, due to the altered concentration and structure of the added component in this region. Our current understanding of the depletion force is based primarily on steric (i.e. hard particle) interactions. However, a much more pronounced effect is possible using charged macromolecular additives; this must be understood/controlled if important applications in colloid/protein crystallization, separation, and bioassay are to be realized. In collaboration with John Walz, we are using atomic force microscopy and molecular computer simulation to understand, predict, and technologically exploit the influence of nanoscale additive charge on the overall colloidal force [32]. The system of study consists of a spherical colloidal particle (of diameter about 10-6 m) near a smooth flat surface in the presence of macro-ions (“nanoparticles” of size about 10-8 m) and micro-ions (atomic-sized counter ions/salt). An important finding is the inverse 1/3 power scaling of the wavelength of the oscillatory force profile with macro-ion density. This scaling persists over a large density range, and involves a prefactor greater than that expected for an isotropic liquid, but less than that of an ordered phase. Understand these confined macro-ion arrangements – which appear to be locally disordered yet ordered on the length scale of the gap region – in terms of macro-ion charge and micro-ion charge screening may contribute to the nanoscale control over colloidal interactions, and ultimately lead to the rational design of new colloid-based methods in separation and detection.

Macro-ion influence on colloidal force



1.             P.R. Van Tassel, Biomolecules at interfaces, in Encyclopedia of Polymer Science and Technology, 3rd Edition. 2003, Wiley Interscience: New York. p. 285-305.

2.             P.R. Van Tassel, L. Guemouri, J.J. Ramsden, G. Tarjus, P. Viot, and J. Talbot, A particle-level model of irreversible protein adsorption with a postadsorption transition. Journal of Colloid and Interface Science, 1998. 207(2): p. 317-323.

3.             S.X. Yang, P. Viot, and P.R. Van Tassel, Generalized model of irreversible multilayer deposition. Physical Review E, 1998. 58(3): p. 3324-3328.

4.             M.A. Brusatori and P.R. Van Tassel, A kinetic model of protein adsorption/surface-induced transition kinetics evaluated by the scaled particle theory. Journal of Colloid and Interface Science, 1999. 219(2): p. 333-338.

5.             J. Talbot, G. Tarjus, P.R. Van Tassel, and P. Viot, From car parking to protein adsorption: an overview of sequential adsorption processes. Colloids and Surfaces a-Physicochemical and Engineering Aspects, 2000. 165(1-3): p. 287-324.

6.             C. Calonder and P.R. Van Tassel, Kinetic regimes of protein adsorption. Langmuir, 2001. 17(14): p. 4392-4395.

7.             P.R. Van Tassel, Statistical mechanical modeling of protein adsorption. Materialwissenschaft Und Werkstofftechnik, 2003. 34(12): p. 1129-1132.

8.             C. Calonder, Y. Tie, and P.R. Van Tassel, History dependence of protein adsorption kinetics. Proceedings of the National Academy of Sciences of the United States of America, 2001. 98(19): p. 10664-10669.

9.             Y. Tie, C. Calonder, and P.R. Van Tassel, Protein adsorption: Kinetics and history dependence. Journal of Colloid and Interface Science, 2003. 268(1): p. 1-11.

10.           Y.R. Tie, A.P. Ngankam, and P.R. Van Tassel, Probing macromolecular adsorbed layer structure and history dependence via the interfacial cavity function. Langmuir, 2004. 20(24): p. 10599-10603.

11.           P.R. Van Tassel, J. Talbot, P. Viot, and G. Tarjus, Distribution function analysis of the structure of depleted particle configurations. Physical Review E, 1997. 56(2): p. R1299-R1301.

12.           P.R. Van Tassel, P. Viot, G. Tarjus, J.J. Ramsden, and J. Talbot, Enhanced saturation coverages in adsorption-desorption processes. Journal of Chemical Physics, 2000. 112(3): p. 1483-1488.

13.           C.R. Wittmer and P.R. Van Tassel, Probing adsorbed fibronectin layer structure by kinetic analysis of monoclonal antibody binding. Colloids and Surfaces B-Biointerfaces, 2005. 41(2-3): p. 103-109.

14.           V. Castells, S.X. Yang, and P.R. Van Tassel, Surface-induced conformational changes in lattice model proteins by Monte Carlo simulation. Physical Review E, 2002. 65(3): p. 031912.

15.           V. Castells and P.R. Van Tassel, Conformational transition free energy profiles of an adsorbed, lattice model protein by multicanonical Monte Carlo simulation. Journal of Chemical Physics, 2005. 122(8): p. 4707.

16.           M.A. Brusatori and P.R. Van Tassel, Biosensing under an applied voltage using optical waveguide lightmode spectroscopy. Biosensors & Bioelectronics, 2003. 18(10): p. 1269-1277.

17.           M.A. Brusatori, Y. Tie, and P.R. Van Tassel, Protein adsorption kinetics under an applied electric field: An optical waveguide lightmode spectroscopy study. Langmuir, 2003. 19(12): p. 5089-5097.

18.           P.R. Van Tassel, Protein adsorption kinetics under an applied electric field, in Encyclopedia of Nanoscience and Nanotechnology. 2004, Dekker. p. 3031-3039.

19.           A.P. Ngankam and P.R. Van Tassel, In situ layer-by-layer film formation kinetics under an applied voltage measured by optical waveguide lightmode spectroscopy. Langmuir, 2005. 21(13): p. 5865-5871.

20.           A.P. Ngankam and P.R. Van Tassel, Continuous polyelectrolyte adsorption under an applied potential. Proceedings of the National Academy of Sciences of the USA, 2006, in press.

21.           C. Calonder, H.W.T. Matthew, and P.R. Van Tassel, Adsorbed layers of oriented fibronectin: A strategy to control cell-surface interactions. Journal of Biomedical Materials Research Part A, 2005. 75A(2): p. 316-323.

22.           A.P. Ngankam, G.Z. Mao, and P.R. Van Tassel, Fibronectin adsorption onto polyelectrolyte multilayer films. Langmuir, 2004. 20(8): p. 3362-3370.

23.           C.R. Wittmer, J.A. Phelps, W.M. Saltzman, and P.R. Van Tassel, Fibronectin terminated multilayer films: protein adsorption and cell attachment studies. Biomaterials, In Press, 2006.

24.           P.R. Van Tassel, Theoretical studies of the available volume for adsorption in a random quenched and depleted disordered medium. Journal of Chemical Physics, 1997. 107(22): p. 9530-9534.

25.           P.R. Van Tassel, Theoretical model of adsorption in a templated porous material. Physical Review E, 1999. 60(1): p. R25-R28.

26.           P.R. Van Tassel, Adsorption in disordered porous materials: theoretical analysis, in Encyclopedia of Surface and Colloid Science. 2002, Dekker: New York. p. 204-211.

27.           L.H. Zhang and P.R. Van Tassel, Theory and simulation of adsorption in a templated porous material: Hard sphere systems. Journal of Chemical Physics, 2000. 112(6): p. 3006-3013.

28.           L.H. Zhang and P.R. Van Tassel, Configurational effects of templating on the adsorption isotherms of templated porous materials. Molecular Physics, 2000. 98(19): p. 1521-1527.

29.           S. Cheng and P.R. Van Tassel, Theory and simulation of the available volume for adsorption in a chain molecule templated porous material. Journal of Chemical Physics, 2001. 114(11): p. 4974-4981.

30.           L.H. Zhang, S.Y. Cheng, and P.R. Van Tassel, Effect of templated quenched disorder on fluid phase equilibrium. Physical Review E, 2001. 64(4): p. 042101.

31.           L. Sarkisov and P.R. Van Tassel, Replica Ornstein-Zernike theory of adsorption in a templated porous material: Interaction site systems. Journal of Chemical Physics, 2005. 123(16): p. 4706.

32.           A. Tulpar, P.R. Van Tassel, and J.Y. Walz, Structuring of macroions confined between like-charged surfaces. Langmuir, 2006. 22(6): p. 2876-2883.