Molecular imprinting is an established method for the creation of artificial recognition sites in synthetic materials through polymerization and cross-linking in the presence of template molecules. Removal of the templates leaves cavities that are complementary to the template molecules in size, shape, and functionality. Although this technique is effective when targeting small molecules, attempts to extend it to larger templates, such as proteins, have failed to show similar success. As opposed to small molecules, proteins are characterized by large size, flexible structure, and large number of functional groups available for recognition, which make it impossible to use imprinting protocols of small molecules for protein imprinting. In this research we use lattice Monte Carlo simulations of an imprinting process using radical polymerization of hydrogels as a simple model for protein-imprinted polymers (PIPs). We investigate the properties of the resulting polymer gel by studying the effects of initiator, cross-linker, and monomer concentrations and the presence of protein on gel structure and porosity. The structure and functionality of the imprinted pore is studied through diffusion of the protein inside the pore immediately following polymerization. The imprinting effect is evaluated by comparing the interaction energy of the protein in the imprinted gel with the energy of a random process.

BackgroundThe balance between self-renewal and differentiation of stem cells is expected to be tightly controlled in order to maintain tissue homeostasis throughout life, also in the face of environmental hazards. Theory, predicting that homeostasis is maintained by a negative feedback on stem cell proliferation, implies a Quorum Sensing mechanism in higher vertebrates.ResultsApplication of this theory to a cellular automata model of stem cell development in disrupted environments shows a sharply dichotomous growth dynamics: maturation within 50-400 cell cycles, or immortalization. This dichotomy is mainly driven by intercellular communication, low intensity of which causes perpetual proliferation. Another driving force is the cells' kinetic parameters. Reduced tissue life span of differentiated cells results in uncontrolled proliferation. Model's analysis, showing that under the Quorum Sensing control, stem cell fraction within a steady state population is fixed, is corroborated by experiments in breast carcinoma cells. Experimental results show that the plating densities of CD44+ cells and of CD44+/24lo/ESA+ cells do not affect stem cell fraction near confluence.ConclusionsThis study suggests that stem cell immortalization may be triggered by reduced intercellular communication, rather than exclusively result from somatic evolution, and implies that stem cell proliferation can be attenuated by signal manipulation, or enhanced by cytotoxics targeted to differentiated cells. In vivo verification and identification of the Quorum Sensing mediating molecules will pave the way to a higher level control of stem cell proliferation in cancer and in tissue engineering.ReviewersThis article was reviewed by Glenn Webb and Marek Kimmel.

Molecular imprinting allows the creation of artificial recognition sites in synthetic materials through polymerization and cross-linking in the presence of template molecules. Removal of the templates leaves cavities that are complementary to the template molecules in size, shape, and functionality. Although this technique is effective when targeting small molecules, attempts to extend it to larger templates, such as proteins, have failed to show similar success. Here we present the second report on our model simulation study of protein imprinting, in which we apply on-lattice Monte Carlo simulations for an imprinting process using radical polymerization of hydrogels as a simple model for protein-imprinted polymers (PIPs). In this part we focus on two gel types: PIPs and templated polymers (TPs), which are polymerized in the presence of charged and neutral proteins, respectively. We calculate the imprinting factor (IF) for gels formed at various conditions and compare it for both gel types. Our results show a significantly higher IF for PIPs, and though the strongest influence on IF is found to be the monomer concentration (Φ), charge concentrations on the protein and in solution also affect IF. The percolation limit of protein-sized pores is found to be a significant turning point for the effect of concentration of functional sites within the gels on IF.

Molecular imprinting has been extensively studied and applied as a simple technique for creating artificial polymer-based recognition gels for a target molecule. Although this technique is effective when targeting small molecules, attempts to extend it to larger templates, such as proteins, have, for the most part, failed to show similar success. Our group has developed a simple simulation model to study protein imprinting. In our previous studies, we investigated the structure of the protein-imprinted pore and imprinting factors of various model proteins. Here, we concentrate on imprinting conditions that affect the separation factor, or the ratio between the interaction energies of the template and a competitor protein. We study the effect of size, charge density, and surface charge distribution of the template protein and calculate the separation factor for various polymerization conditions. Our model captures the known effect of increasing imprinting factor (ratio of binding of the protein in an imprinted polymer to that of a nonimprinted polymer) with increasing surface functionality of the polymer but at the cost of reduced selectivity. Most interestingly, we observe that the surface charge distribution of the protein plays an important role in selectivity of the protein-imprinted polymer, suggesting that some proteins may be better candidates for molecularly imprinted polymers than others.

Molecular imprinting is an established method for the creation of artificial recognition sites in synthetic materials through polymerization and cross-linking in the presence of template molecules. Removal of the templates leaves cavities that are complementary to the template molecules in size, shape, and functionality. In recent years, various theoretical and computational models have been developed as tools to aid in the design of molecularly imprinted polymers (MIPs) or to provide insight into the features that determine MIP performance. These studies can be grouped into two general approaches-screening for possible functional monomers for particular templates and macromolecular models focusing on the structural characterization of the imprinted material. In this review, we pay special attention to coarse-grained models that characterize the functional heterogeneity in imprinted pores, but also cover recent advances in atomistic and first principle studies. We offer a critical assessment of the potential impact of the various models towards improving the state-of-the-art of molecular imprinting.