Biological hydrogels as selective diffusion barriers

Abstract

The controlled exchange of molecules between organelles, cells, or organisms and their environment is crucial for life. Biological gels such as mucus, the extracellular matrix (ECM), and the biopolymer barrier within the nuclear pore are well suited to achieve such a selective exchange, allowing passage of particular molecules while rejecting many others. Although hydrogel-based filters are integral parts of biology, clear concepts of how their barrier function is controlled at a microscopic level are still missing. We summarize here our current understanding of how selective filtering is established by different biopolymer-based hydrogels. We ask if the modulation of microscopic particle transport in biological hydrogels is based on a generic filtering principle which employs biochemical/biophysical interactions with the filtered molecules rather than size-exclusion effects.

Figure 1

The cell membrane/hydrogel barrier. Eukaryotic cells are surrounded by a plasma membrane, which mediates both compartmentation and the exchange of material with the extracellular space. This plasma membrane is typically externally coated with a hydrogel such as the extracellular matrix or mucus, which provides an additional permeability barrier. For example, extracellular hydrogels can prevent molecules or microscopic particles such as viruses or bacteria from reaching the plasma membrane. The detailed microscopic mechanisms by which macromolecules or pathogens are retained by biological hydrogels are still poorly understood.

Figure 2

Biopolymer based hydrogels control the translocation of microscopic objects and act as selective permeability filters. They allow the passage of certain molecules (green) whereas rejecting others (orange). (A) The epithelium is lined with a layer of mucin polymers, which form a hydrogel that shields the underlying cell layer from infectious agents such as viruses or bacteria. (B) Extracellular matrix systems such as the basal lamina or the connective tissue regulate the passage of molecules to and from the blood stream or between cells. (C) Nuclear pores are filled with nucleoporin polymers, which regulate the import and export of proteins into or out of the nucleus. (D) In bacterial biofilms, extracellular polymers effectively shield the bacteria from antibiotics while allowing nutrients to enter the biofilm. (E) The vitreous humour in the mammalian eye allows the penetration of certain antibiotics while blocking others.

Figure I

Microscopic particles can probe different hydrogel parameters. (A) Inert particles (green) that are small enough can diffuse inside the hydrogel matrix where they experience a local viscosity that is mainly dictated by the hydrogel solvent. (B) Particles that bind to hydrogel components (orange) will not be able to fully explore the local microenvironment and thus cannot report the correct hydrogel mesh size. (C) Large particles that are geometrically trapped in the hydrogel mesh will report the local viscoelasticity of the hydrogel and thus provide mechanical information about the hydrogel rather than probing its microstructure.

Figure II

Two generic filtering principles can be employed by biopolymer based hydrogels: (A) Size filtering allows particles that are smaller than the cut-off size of the hydrogel to pass while larger objects are rejected. (B) Interaction filtering allows for distinguishing particles according to their surface properties: A subset of particles (orange) strongly interacts with the polymer matrix of the hydrogel and is trapped, while other particles (green) show only weak interactions and thus are allowed to pass.

Figure III

Binding interactions of diffusing molecules with hydrogel polymers could help establish and maintain gradients. In the absence of such interactions with the hydrogel, locally secreted molecules such as signalling molecules or growth factors would quickly spread by diffusion and cover a large area around the source cell. In contrast, when those molecules are trapped in the surrounding hydrogel polymer matrix by absorption events, they can locally accumulate and form a gradient. If those binding interactions are weakened, these gradients can be dissolved and the stored molecules are released without requiring enzymatic degradation of the polymer matrix.