title: Polymer surface functionalities that control human embryoid body cell adhesion revealed by high throughput surface characterization of combinatorial material microarrays.
abstract: High throughput materials discovery using combinatorial polymer microarrays to screen for new biomaterials with new and improved function is established as a powerful strategy. Here we combine this screening approach with high throughput surface characterization (HT-SC) to identify surface structure-function relationships. We explore how this combination can help to identify surface chemical moieties that control protein adsorption and subsequent cellular response. The adhesion of human embryoid body (hEB) cells to a large number (496) of different acrylate polymers synthesized in a microarray format is screened using a high throughput procedure. To determine the role of the polymer surface properties on hEB cell adhesion, detailed HT-SC of these acrylate polymers is carried out using time of flight secondary ion mass spectrometry (ToF SIMS), X-ray photoelectron spectroscopy (XPS), pico litre drop sessile water contact angle (WCA) measurement and atomic force microscopy (AFM). A structure-function relationship is identified between the ToF SIMS analysis of the surface chemistry after a fibronectin (Fn) pre-conditioning step and the cell adhesion to each spot using the multivariate analysis technique partial least squares (PLS) regression. Secondary ions indicative of the adsorbed Fn correlate with increased cell adhesion whereas glycol and other functionalities from the polymers are identified that reduce cell adhesion. Furthermore, a strong relationship between the ToF SIMS spectra of bare polymers and the cell adhesion to each spot is identified using PLS regression. This identifies a role for both the surface chemistry of the bare polymer and the pre-adsorbed Fn, as-represented in the ToF SIMS spectra, in controlling cellular adhesion. In contrast, no relationship is found between cell adhesion and wettability, surface roughness, elemental or functional surface composition. The correlation between ToF SIMS data of the surfaces and the cell adhesion demonstrates the ability to identify surface moieties that control protein adsorption and subsequent cell adhesion using ToF SIMS and multivariate analysis.
authors.affiliation: Laboratory of Biophysics and Surface and Analysis, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Mei
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Hook
authors.forename: Michael
authors.initials: M
authors.lastname: Taylor
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Urquhart
authors.forename: Said R
authors.initials: SR
authors.lastname: Bogatyrev
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
authors.forename: Martyn C
authors.initials: MC
authors.lastname: Davies
authors.forename: Morgan R
authors.initials: MR
authors.lastname: Alexander
mesh_terms: D000327:Adsorption; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004602:Elements; D058732:Embryoid Bodies / Q000166:cytology* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D016018:Least-Squares Analysis; D051379:Mice; D046228:Microarray Analysis / Q000379:methods*; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D025341:Principal Component Analysis; D015203:Reproducibility of Results; D018629:Spectrometry, Mass, Secondary Ion; D013059:Spectrum Analysis, Raman; D013329:Structure-Activity Relationship; D013499:Surface Properties; D017155:Wettability
chemical_list: D004602:Elements; D005353:Fibronectins; D011108:Polymers