A microfluidics approach to study the selective permeability of native and chemically modified mucin gels
Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
Final Report Abstract
In this project, the binding processes contributing to the selective permeability properties of mucin hydrogels were investigated. We performed a structure-function analysis of the mucin glycoproteins, and identified critical parameters that affect the selective permeability properties of mucin hydrogels as well their ability to form hydrogels. First, a suitable microfluidics setup was developed, which allowed for quantifying molecular penetration events into mucin hydrogels. With this experimental platform, the permeability properties of mucin/buffer interfaces towards molecular probes with tailored properties were assessed. The impact of both, electrostatic forces and hydrophobic interactions, was demonstrated by using dextran species with different charge properties as well as a set of synthetic peptides. The obtained experimental data was rationalized with a theoretical description of the molecular transport process based on diffusion-reaction equations. With this model, it was possible to make predictions on the penetration and translocation efficiency of different chemical objects (such as drug molecules) across mucin gels. Moreover, the penetration behavior of mucin hydrogels by a patho-physiologically relevant protein, α-synuclein, was investigated. Here, we observed that this particular molecule can alter the microarchitecture of the mucin gels via binding to the mucins, and this effect weakens the barrier properties of the mucin gels. Finally, we analyzed the molecular binding events occurring with mucins in more detail, and deciphered the contribution of different structural motifs of mucins on this process. Here, conformational changes in the mucin molecule upon removal of charged moieties from the mucin backbone was identified as an additional phenomenon that may affect the barrier properties of mucin systems in vivo as well, e.g., when pathogens attack the structural integrity of mucin glycoproteins.
Publications
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Transient binding promotes molecule penetration into mucin hydrogels by enhancing molecular partitioning, Biomaterials Science. 6, 3373 - 3387 (2018)
M. Marczynski, B.T. Käsdorf, B. Altaner, A. Wenzler, U. Gerland, and O. Lieleg
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Alpha-Synuclein penetrates mucin hydrogels despite its mucoadhesive properties, Biomacromolecules. 20 (12) 4332-4344 (2019)
M. Marczynski, C. Rickert, S. Semerdzhiev, W. van Dijk, I. Segers-Nolten, M.M.A.E. Claessens, and O. Lieleg
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Charged glycan residues critically contribute to the adsorption and lubricity of mucins, Colloids and Surfaces B: Biointerfaces. 187, 110614 (2020)
M. Marczynski, B.N. Balzer, K. Jiang, T.M. Lutz, T. Crouzier, and O. Lieleg
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Repulsive backbonebackbone interactions modulate access to specific and unspecific binding sites on surface-bound mucins, Langmuir. 36 (43) 12973-12982 (2020)
T.M. Lutz, M. Marczynski, M. Grill, W.A. Wall, and O. Lieleg
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Advances in Mucin Biopolymer Research: Purification, Characterization, and Applications. Book chapter in: Biopolymers for Biomedical and Biotechnological Applications, edited by Bernd Rehm and M. Fata Moradali (2021)
M. Marczynski, B. Winkeljann, and O. Lieleg
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Purified mucins in drug delivery research, Advanced Drug Delivery Reviews, 58, 102363 (2021)
M. Marczynski, C. Kimna and O. Lieleg
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Structural alterations of mucins are associated with losses in functionality, Biomacromolecules, 22 (4), 1600-1613 (2021)
M. Marczynski, K. Jiang, M. Blakeley, V. Srivastava, F. Vilaplana, T. Crouzier, and O. Lieleg
