Thermoresponsive Microgel Coatings as Versatile Functional Compounds for Novel Cell Manipulation Tools

Abstract

Abstract:For the effective use of live cells in biomedicine as in vitro test systems or in biotechnology, non-invasive cell processing and characterisation are key elements. Thermoresponsive polymer coatings have been demonstrated to be highly beneficial for controlling the interaction of adherent cells through their cultivation support. However, the widespread application of these coatings is hampered by limitations in their adaptability to different cell types and because the full range of applications has not yet been fully explored. In the work presented here, we address these issues by focusing on three different aspects. With regard to the first aspect, by using well-defined laminar flow in a microchannel, a highly controllable and reproducible shear force can be applied to adherent cells. Employing this tool, we demonstrate that cells can be non-invasively detached from a support using a defined shear flow. The second aspect relates to the recent development of simple methods for patterning thermoresponsive coatings. Here, we show how such patterned coatings can be used for improving the handling and reliability of a wound-healing assay. Two pattern geometries are tested using mouse fibroblasts and CHO cells. In terms of the third aspect, the adhesiveness of cells depends on the cell type. Standard thermoresponsive coatings are not functional for all types of cells. By coadsorbing charged nanoparticles and thermoresponsive microgels, it is demonstrated that the adhesion and detachment behaviour of cells on such coatings can be modulated.

Contrast variation SANS measurement of shell monomer density profiles of smart core–shell microgels

“…The response of these materials has great potential in the context of different applications like smart catalyst carriers, [11][12][13] drug delivery, 14,15 sensors, [16][17][18] optical devices, [19][20][21] responsive surface coatings 22 and actuators 23 or in biomedical applications. 24 Combining two monomers of different transition temperatures in statistical copolymers can be used to tune the swelling transition temperature, [25][26][27][28][29] whereas the subsequent synthesis of core and then shell 27,30-35 may lead to a continuous, linear temperature dependent swelling. 27,36,37 The linearity of the response of these coreshell systems might be beneficial especially for sensors and actuators.…”

Importance of pH in Synthesis of pH-Responsive Cationic Nano- and Microgels

“…Their increasing popularity can be attributed to their responsiveness towards external stimuli such as temperature or pH, which is achieved by polymerizing certain monomers such as acrylamides and weak acids or bases [ 9 , 10 , 11 , 12 , 13 , 14 ] and due to their tunability in size [ 15 ] and architecture [ 16 , 17 , 18 , 19 ]. A rapid change in size upon changing these stimuli enables a vast variety of possible applications in the fields of catalysis, sensing, drug targeting, surface-functionalization or bio-conjugation [ 7 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. The latter is often mentioned together with cationic nano- and microgels that are far less studied than their anionic counterparts [ 25 ].…”

Temperature‐Controlled Adhesion to Carbohydrate Functionalized Microgel Films: An E. coli and Lectin Binding Study

“…[ 38,41,42,43 ] The temperature dependent shifts in the microgels’ elastic modulus and surface roughness can be used to create switchable cell culture surfaces that enable the controlled attachment and detachment of cells even without addressing specific cell adhesion receptors. [ 35,40,44 ] However, microgel coatings specifically targeting selected cells, e.g. bacteria via lectin binding have not been studied so far.…”