Polymer chain collapse induced by many-body dipole correlations

We present a simple analytical theory of a flexible polymer chain dissolved in a good solvent, carrying permanent freely oriented dipoles on the monomers. We take into account the dipole correlations within the random phase approximation (RPA), as well as a dielectric heterogeneity in the internal polymer volume relative to the bulk solution. We demonstrate that the dipole correlations of monomers can be taken into account as pairwise ones only when the polymer chain is in a coil conformation. In this case the dipole correlations manifest themselves through the Keesom interactions of the permanent dipoles. On the other hand, the dielectric heterogeneity effect (dielectric mismatch effect) leads to the effective interaction between the monomers of the polymeric coil. Both of these effects can be taken into account by renormalizing the second virial coefficient of the monomer-monomer volume interactions. We establish that in the case when the solvent dielectric permittivity exceeds the dielectric permittivity of the polymeric material, the dielectric mismatch effect competes with the dipole attractive interactions, leading to polymer coil expansion. In the opposite case, both the dielectric mismatch effect and the dipole attractive interaction lead to the polymer coil collapse. We analyse the coil-globule transition caused by the dipole correlations of monomers within the many-body theory. We demonstrate that accounting for the dipole correlations higher than the pairwise ones smooths this pure electrostatics driven coil-globule transition of the polymer chain

A statistical theory of coil-to-globule-to-coil transition of a polymer chain in a mixture of good solvents

We present an off-lattice statistical model of a single polymer chain in mixed-solvent media. Taking into account the polymer conformational entropy, renormalization of solvent composition near the polymer backbone, the universal intermolecular excluded-volume and van der Waals interactions within the self-consistent field theory, the reentrant coil-to-globule-to-coil transition (co-nonsolvency) has been described in this paper. For convenience we split the system volume in two parts: the volume occupied by the polymer chain and the volume of bulk solution. Considering the equilibrium between two sub-volumes, the polymer solvation free energy as a function of radius of gyration and co-solvent mole fraction within internal polymer volume has been obtained. Minimizing the free energy of solvation with respect to its arguments, we show two qulitatively different regimes of co-nonsolvency. Namely, at sufficiently high temperature the reentrant coil-to-globule-to-coil transition proceeds smoothly. On the contrary, when the temperature drops below a certain threshold value a coil-globule transition occurs in the regime of first-order phase transition, i.e., discontinuous changes of the radius of gyration and the local co-solvent mole fraction near the polymer backbone. We show that, when the collapse of the polymer chain takes place, the entropy and enthalpy contributions to the solvation free energy of the globule strongly grow. From the first principles of statistical thermodynamics we confirm earlier speculations based on the MD simulations results that the co-nonsolvency is the essentially enthalpic-entropic effect and is caused by enthalpy-entropy compensation. We show that the temperature dependences of the solution heat capacity change due to the solvation of the polymer chain are in qualitative agreement with the differential scanning calorimetry data for PNIPAM in aqueous methanol

Inhibition of Decay-Accelerating Factor (CD55) Attenuates Prostate Cancer Growth and Survival In Vivo

Decay-accelerating factor (CD55) is a member of membrane-bound complement-regulatory proteins. CD55 expression correlates with poor survival in patients with colorectal cancer and has been implicated in the survival and tumorigenesis of blood-borne malignancies. Histologic analysis of clinical specimens from patients with advanced prostate cancer revealed an increase in CD55 expression in prostate tumor epithelial cells. CD55 was shown to be functionally active and to inhibit complement-mediated lysis in PC-3 and DU145 cells. The percentage of lysis was correlative with the CD55 expression profile observed in these prostate cancer cell lines. These data suggest that CD55 is an important regulator of prostate cancer cell survival. As a result, we have hypothesized that CD55 expression on prostate cancer cells promotes cell survival and contributes to the metastatic potential of prostate cancer cells. To determine the role of CD55 in prostate cancer tumorigenesis and metastasis, we generated PC-3(Luc) prostate cancer cells with CD55 siRNA-targeted disruption. We found that PC-3(Luc)/CD55 siRNA constructs in SCID mice resulted in a significant attenuation of overall tumor burden. Further investigation into the mechanisms of CD55-mediated tumor cell/microenvironment interaction is necessary to understand the role of CD55 in tumor cell survival and metastatic lesion formation

Genomic characterization of human SEC14L1 splice variants within a 17q25 candidate tumor suppressor gene region and identification of an unrelated embedded expressed sequence tag

Human SEC14L1 shows partial sequence homology to the budding yeast SEC14 protein and the Japanese flying squid retinal-binding protein and was previously generally localized to 17q25. We more precisely mapped SEC14L1 within a discrete region of 17q25 that likely harbors at least one putative breast and ovarian tumor suppressor gene. We determined that this gene consists of 18 exons ranging in size from 70 bp (exon 11) to 3088 bp (exon 17) and spanning at least 58 kb of DNA. Exon 17 contained a highly polymorphic variable number of tandem repeats (VNTR) and was present only in the larger ubiquitously expressed 5.5-kb transcript. The 3.0-kb ubiquitously expressed transcript included sequences at the beginning of exon 17 (designated exon 17a) and the end of exon 17 (designated exon 18), but lacked the internal 2439 bp of exon 17, including the VNTR. This alternative splicing resulted in a predicted protein of 719 residues from the smaller transcript with four more terminal amino acids than the 715 residue protein predicted from the larger transcript. EST H49244 spanned exon 11 of SEC14L1 and was specifically expressed in human peripheral blood leukocytes. One intragenic single nucleotide polymorphism (SNP) was confirmed. SEC14L1 contained the CRAL/TRIO domain also found in alpha-tocopherol transfer protein (TTPA) and cellular retinaldehyde-binding protein (CRALBP). As retinoids have been shown to inhibit the growth of breast cancer cells, loss of the proposed SEC14L1 retinal-binding function may contribute to breast tumorigenesis. As TTPA and CRALBP have been implicated in retinitis pigmentosa (RP), altered SEC14L1 expression may contribute to RP in previously unlinked families. Coding exon-specific PCR primers were designed to aid in future expression and mutational analyses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42124/1/335-12-12-925_10120925.pd