The spatial elastic modulus distribution of microgel networks in presence and absence of bifunctional crosslinkers is studied by AFM. Thermoresponsive poly(N-isopopylacrylamide) (PNIPAM) and poly(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) methacrylate)) (P(MEO2MA-co-OEGMA)) microgel are...
Adhesion processes at the cellular
scale are dominated by carbohydrate
interactions, including the attachment and invasion of pathogens.
Carbohydrate-presenting responsive polymers can bind pathogens and
inhibit pathogen invasion by remote stimuli for the development of
new antibiotic strategies. In this work, the adhesion forces of E. coli to monolayers composed of mannose-functionalized
microgels with thermosensitive poly(N-isopropylacrylamide)
(PNIPAM) and poly(oligo(ethylene glycol)) (PEG) networks are quantified
using single-cell force spectroscopy (SCFS). When exceeding the microgels’
lower critical solution temperature (LCST), the adhesion increases
up to 2.5-fold depending on the polymer backbone and the mannose density.
For similar mannose densities, the softer PNIPAM microgels show a
significantly stronger adhesion increase when crossing the LCST as
compared to the stiffer PEG microgels. This is explained by a stronger
shift in swelling, mannose density, and surface roughness of the softer
gels when crossing the LCST. When using nonbinding galactose instead
of mannose, or when inhibiting bacterial receptors, a certain level
of adhesion remains, indicating that also polymer–fimbria entanglements
contribute to adhesion. The presented quantitative analysis provides
insights into carbohydrate-mediated bacterial adhesion and the relation
to material properties and shows the prospects and limitations of
interactive polymer materials to control the attachment of bacteria.
This study aims at quantifying the steric shielding effect of multivalent glycoconjugates targeting pathogens by blocking their carbohydrate binding sites. Specifically, PEGylated and non-PEGylated glycoconjugates are studied as inhibitors of lectins and bacterial adhesins evaluating the steric repulsion effect of the nonbinding PEG chains. We use the soft colloidal probe (SCP) adhesion assay to monitor the change in the adhesion energy of mannose (Man)decorated hydrogel particles on a layer of concanavalin A (ConA) in the presence of sequence-defined multivalent glycoconjugate inhibitors over time. The results show that PEGylated glycoconjugates achieve a stronger adhesion inhibition when compared to non-PEGylated glycoconjugates although the dissociation constants (K D ) of the PEGgylated compounds to ConA were larger. These results appear in line with Escherichia coli adhesion inhibition assays showing a small increase of bacteria detachment by PEGgylated glycoconjugates compared to non-PEGylated compounds. This suggests that an increase of sterical shielding via PEGylation may help reduce the invasiveness of pathogens even after they have adhered. Adhesion studies based on electrostatic interactions using amine-linked PEG of varying molecular weight confirm that such sterical shielding effect is not limited to carbohydrate-mediated adhesion.
The detection of tumor cells from liquid biopsy samples is of critical importance for early cancer diagnosis, malignancy assessment, and treatment. In this work, coatings of hyaluronic acid (HA)-functionalized dualstimuli responsive poly(N-isopropylacrylamide) (PNIPAM) microgels are used to study the specificity of breast cancer cell binding and to assess cell friendly release mechanisms for further diagnostic procedures. The microgels are established by straightforward precipitation polymerization with amine bearing comonomers and postfunctionalization with a UV-labile linker that covalently binds HA to the microgel network. Well-defined microgel coatings for cell binding are established via simple physisorption and annealing. The HA-presenting PNIPAM microgel films are shown to specifically adhere CD44 expressing breast cancer cell lines (MDA-MB-231 and MCF-7), where an increase in adhesion correlates with higher CD44 expression and HA functionalization. Upon cooling below the lower critical solution temperature of PNIPAM microgels, the cells could be released; however, 10−30% of the cells still remained on the surface even after prolonged cooling and mild mechanical agitation. A complete cell release is achieved after applying the light stimulus by short UV treatment cleaving HA units from the microgels. Owing to the comparatively straightforward preparation procedures, such dual-responsive microgel films could be considered for the effective capture, release, and diagnostics of tumor cells.
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