Tai-Hsi Fan

A Biocompatible and Biodegradable Protein Hydrogel with Green and Red Autofluorescence: Preparation, Characterization and In Vivo Biodegradation Tracking and Modeling

Because of its good biocompatibility and biodegradability, albumins such as bovine serum albumin (BSA) and human serum albumin (HSA) have found a wide range of biomedical applications. Herein, we report that glutaraldehyde cross-linked BSA (or HSA) forms a novel fluorescent biological hydrogel, exhibiting new green and red autofluorescence in vitro and in vivo without the use of any additional fluorescent labels. UV-vis spectra studies, in conjunction with the fluorescence spectra studies including emission, excitation and synchronous scans, indicated that three classes of fluorescent compounds are presumably formed during the gelation process. SEM, FTIR and mechanical tests were further employed to investigate the morphology, the specific chemical structures and the mechanical strength of the as-prepared autofluorescent hydrogel, respectively. Its biocompatibility and biodegradability were also demonstrated through extensive in vitro and in vivo studies. More interestingly, the strong red autofluorescence of the as-prepared hydrogel allows for conveniently and non-invasively tracking and modeling its in vivo degradation based on the time-dependent fluorescent images of mice. A mathematical model was proposed and was in good agreement with the experimental results. The developed facile strategy to prepare novel biocompatible and biodegradable autofluorescent protein hydrogels could significantly expand the scope of protein hydrogels in biomedical applications.

Scaling of nanoparticle retardation in semi-dilute polymer solutions

We analyze the scaling law for the polymer-induced retardation a nanoparticle experiences as it moves through a semi-dilute polymer solution. The translational friction is calculated from a modified Stokes flow using a local viscosity near the nanosphere. The results rationalize a general retardation factor, R = exp(Kaµcν) [T. Odijk, Biophys. J., 2000, 79, 2314], revealing scaling exponents µ = 0.77 and ν = 1, which are in agreement with experiment. We find that rotational motion also has a self-similar behavior and R can be described too by a stretched exponential with slightly different exponents.

Hydrodynamic interaction of two colloids in nonadsorbing polymer solutions

The hydrodynamic interaction between two colloids mediated by non-adsorbing polymer chains is considered for spherical colloids moving along the symmetric line. We present a resistance analysis and determine the mobility function that incorporates the polymer depletion effect. The hydrodynamic friction is calculated by solving the Stokes equation with non-uniform viscosity using the vorticity-stream function method and a bispherical coordinate transformation. The numerical results show the effective viscosity asymptotically approaches the single sphere limit of Fan et al. (T.-H. Fan, B. Xie and R. Tuinier, Phys. Rev. E., 2007, 76, 051405) for a large interparticle distance. As the particles get closer the effective viscosity decreases and finally approaches the lubrication limit, where the friction equals that of two close-approached spheres in a pure solvent. The flow analysis shows that the circulation pattern, a characteristic for the presence of the depletion layer, expands upon approach of the particles. The pressure contribution to the total drag force is determined by a competition between the lubrication force and the apparent slip effect caused by overlap of the depletion layers. The friction of the single sphere limit is only attained in the limit of an extremely small colloid volume fractions. Our results help rationalize the long-time relative diffusivity of Brownian particles in polymer solutions and this is important for a better understanding of the depletion-induced demixing kinetics.

Electrohydrodynamics and surface force analysis in AFM imaging of a charged, deformable biological membrane in a dilute electrolyte solution

Surface forces arising in atomic force microscopy (AFM) imaging of a deformable, negatively charged biological membrane in an electrolyte solution are investigated in the limit of continuous electrohydrodynamics. Specifically, we extend our previous analysis (Fan, T.-H.; Fedorov, A. G. Langmuir 2003, 19, 1347−1356) of purely hydrodynamic interactions between an AFM tip and the elastic cell membrane by accounting for electric double-layer forces under the assumptions of a dilute electrolyte solution and local electrochemical equilibrium. The solution of the problem is obtained by integrating the quasi-steady, electrically forced Stokes equation for the electrohydrodynamic field, the linearized Poisson−Boltzmann equation for the electrostatic field in the electrolyte inside and outside of the cell, and the Laplace equation for the electrostatic field within a dielectric AFM tip. Helfrich and Zhong-cans equation for an equilibrium shape of the cell membrane is employed as a quasi-steady, nonlinear boundary ...

Lipid-based nanodiscs as models for studying mesoscale coalescence – a transport limited case

Lipid-based nanodiscs (bicelles) are able to form in mixtures of long- and short-chain lipids. Initially, they are of uniform size but grow upon dilution. Previously, nanodisc growth kinetics have been studied using time-resolved small angle neutron scattering (SANS), a technique which is not well suited for probing their change in size immediately after dilution. To address this, we have used dynamic light scattering (DLS), a technique which permits the collection of useful data in a short span of time after dilution of the system. The DLS data indicate that the negatively charged lipids in nanodiscs play a significant role in disc stability and growth. Specifically, the charged lipids are most likely drawn out from the nanodiscs into solution, thereby reducing interparticle repulsion and enabling the discs to grow. We describe a population balance model, which takes into account Coulombic interactions and adequately predicts the initial growth of nanodiscs with a single parameter - i.e., surface potential. The results presented here strongly support the notion that the disc coalescence rate strongly depends on nanoparticle charge density. The present system containing low-polydispersity lipid nanodiscs serves as a good model for understanding how charged discoidal micelles coalesce.

Radiative transfer in a semitransparent hemispherical shell

Radiative transfer in a semitransparent hemispherical shell placed on an opaque surface is simple yet realistic representation of the heating process encountered in various materials processing applications ranging from metallurgical slag foaming to batch foams in glass melting to hollow bead fabrication. The objective of this paper is to develop fundamental understanding and predictive models for the apparent radiative properties of a hemispherical shell exposed to incident collimated radiation. Both analytical and numerical results are obtained and compared against each other for the purpose of validation of an analytical model. The study provides fundamental information on radiative transfer in a semitransparent hemispherical shell as well as presents an effective numerical algorithm to calculate the local intensity field and thus the local volumetric heating in the shell.

Thermal softening of superswollen polyelectrolyte microcapsules

We study the effect of temperature on the mechanical properties of polyelectrolyte microcapsules assembled by layer-by-layer (LbL) deposition of polystyrene sulfonate (PSS)/polyallylamine hydrochloride (PAH). Capsules are initially significantly swollen (superswollen) as a result of the osmotic effect caused by in situpolymerization of inner PSS. It is well known that hollow PSS/PAH microcapsules are insensitive to temperature changes. However, we show that the heat treatment of superswollen capsules introduces additional plastic deformation and leads to an additional softening of a highly stretched polyelectrolyte shell. A simple model is provided to characterize the elasto-plastic behavior of the microcapsules under consideration. This finding suggests an alternative method to control mechanical properties of the multilayer shell.

Repetitive Biomimetic Self-healing of Ca(2+)-Induced Nanocomposite Protein Hydrogels.

Self-healing is a capacity observed in most biological systems in which the healing processes are autonomously triggered after the damage. Inspired by this natural behavior, researchers believed that a synthetic material possessing similar self-recovery capability could also be developed. Albeit various intrinsic self-healing systems have been developed over the past few decades, restriction on the biocompatibility due to the required synthetic conditions under extreme pH and with poisonous cross-linker significantly limits their application in biomedical field. In this study, a highly biocompatible nanocomposite protein hydrogel with excellent biomimetic self-healing property is presented. The self-healing protein gel is made by inducing calcium ions into the mixture of heat-induced BSA nano-aggregates and pristine BSA molecules at room temperature and under physiological pH due to the ion-mediated protein-protein association and the bridging effect of divalent Ca2+ ions. The as-prepared protein hydrogel shows excellent repetitive self-healing properties without using any external stimuli at ambient condition. Such outstanding self-recovery performance was quantitatively evaluated/validated by both dynamic and oscillatory rheological analysis. Moreover, with the presence of calcium ions, the self-healing behavior can be significantly facilitated/enhanced. Finally, the superior biocompatibility demonstrated by in vitro cytotoxicity analysis suggests that it is a promising self-healing material well-suited for biomedical applications.

An aptamer-functionalized hydrogel for controlled protein release: A modeling study

An analytical model is developed for predicting the controlled release of platelet-derived growth factor-BB (PDGF-BB) from an aptamer-functionalized hydrogel. The release kinetics are determined by the equilibrium constant of aptamer–protein interactions, which significantly increases the characteristic release time scale. The reduction of the cumulative protein release can also be modulated by tuning the binding affinity of the aptamer. The analysis describes the underlying transport and reaction mechanisms for the controlled protein release well. Particularly, the non-Fickian release kinetics are represented by a self-similar release profile. The model is validated by experiments and direct numerical calculation. It can be applied to release kinetics involving multiple aptamers and proteins.

Novel green and red autofluorescent protein nanoparticles for cell imaging and in vivo biodegradation imaging and modeling

Albumins are widely used in bioengineering due to their low-cost, good biocompatibility and biodegradability. Herein we report that cross-linked bovine serum albumin (BSA) forms a suspension of novel fluorescent nanoparticles with an average size of ∼40 nm, exhibiting strong green/red autofluorescence. UV-vis spectra, in conjunction with fluorescence emission spectra, suggest that three classes of fluorescent compounds presumably formed during the preparation. The size distribution and surface morphology of the autofluorescent BSA nanoparticles were characterized using various advanced techniques. After removal of excessive cross-linking agent through dialysis, the autofluorescent BSA nanoparticles were first demonstrated for cell bioimaging application using 293FT human kidney cell line. Its good biocompatibility and low cytotoxicity were further validated by an in vitro cytotoxicity assay and an in vivo histological study. The strong red autofluorescence of the BSA nanoparticles was further exploited in the realization of convenient and non-invasive tracking/modeling of its in vivo degradation based on real-time fluorescence imaging. A mathematical model was proposed and in good agreement with the experimental results. This study indicates that the as-prepared functional, biocompatible and biodegradable autofluorescent protein nanoparticles are suitable for a range of biomedical applications.