title: Signaling factor interactions with polysaccharide aggregates of bacterial biofilms.
abstract: Biofilms are surface-attached colonies of bacteria embedded in an extracellular polymeric substance (EPS). Inside the eukaryotic hosts, bacterial biofilms interact with the host cells through signaling factors (SFs). These signaling processes play important roles in the interaction between bacteria and host cells and the outcome of infections and symbiosis. However, how host immune factors diffuse through biofilms is not well understood. Here, we describe synergistic molecular dynamics and experimental approaches for studying the translocation of signaling factors through polysaccharide chain aggregates present in the extracellular matrix of bacterial biofilms. The effect of polysaccharide chain degradation on the energetics of SF-EPS interactions was examined by simulating an EPS consisting of various polysaccharide chain lengths. It is shown that the SF stabilization energy, defined as the average potential of mean force difference between the environments outside and within the matrix, increases linearly with decreasing chain length. This effect has been explained based on the changes in the polysaccharide configurations around the SF. Specifically, shorter chains are packed tightly around the SF, promoting favorable SF-EPS interactions, while longer chains are packed loosely resulting in screening of interactions with neighboring chains. We further investigated the translocation of SFs through the host cell membrane using molecular dynamics simulations. Further, simulations predict the existence of energy barriers greater than 1000 kJ mol(-1) associated with the translocation of the signaling factors necrosis factor-alpha (TNF-α) and granulocyte macrophage colony stimulating factor (GM-CSF) across the lipid bilayer. The agreement of computational and experimental findings motivates future computational studies using a more detailed description of the EPS aimed at understanding the role of the extracellular matrix on biofilm drug resistance.
authors.affiliation: Department of Biomedical and Chemical Engineering, §Department of Civil and Environmental Engineering, ∥Department of Biology, ⊥Department of Physics, ‡Syracuse Biomaterials Institute, Syracuse University , Syracuse, New York 13244, United States.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: DeSalvo
authors.forename: Yating
authors.initials: Y
authors.lastname: Liu
authors.forename: Geetika Sanjay
authors.initials: GS
authors.lastname: Choudhary
authors.forename: Dacheng
authors.initials: D
authors.lastname: Ren
authors.forename: Shikha
authors.initials: S
authors.lastname: Nangia
authors.forename: Radhakrishna
authors.initials: R
authors.lastname: Sureshkumar
mesh_terms: D001419:Bacteria / Q000166:cytology* / Q000378:metabolism*; D018441:Biofilms; D002462:Cell Membrane / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D011487:Protein Conformation; D015398:Signal Transduction; D013816:Thermodynamics; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000378:metabolism
chemical_list: D003911:Dextrans; D011135:Polysaccharides, Bacterial; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor