title: Analysis of high-throughput screening reveals the effect of surface topographies on cellular morphology.
abstract: Surface topographies of materials considerably impact cellular behavior as they have been shown to affect cell growth, provide cell guidance, and even induce cell differentiation. Consequently, for successful application in tissue engineering, the contact interface of biomaterials needs to be optimized to induce the required cell behavior. However, a rational design of biomaterial surfaces is severely hampered because knowledge is lacking on the underlying biological mechanisms. Therefore, we previously developed a high-throughput screening device (TopoChip) that measures cell responses to large libraries of parameterized topographical material surfaces. Here, we introduce a computational analysis of high-throughput materiome data to capture the relationship between the surface topographies of materials and cellular morphology. We apply robust statistical techniques to find surface topographies that best promote a certain specified cellular response. By augmenting surface screening with data-driven modeling, we determine which properties of the surface topographies influence the morphological properties of the cells. With this information, we build models that predict the cellular response to surface topographies that have not yet been measured. We analyze cellular morphology on 2176 surfaces, and find that the surface topography significantly affects various cellular properties, including the roundness and size of the nucleus, as well as the perimeter and orientation of the cells. Our learned models capture and accurately predict these relationships and reveal a spectrum of topographies that induce various levels of cellular morphologies. Taken together, this novel approach of high-throughput screening of materials and subsequent analysis opens up possibilities for a rational design of biomaterial surfaces.
authors.affiliation: Delft Bioinformatics Lab, Delft University of Technology, Mekelweg 4, Delft 2628 CD, The Netherlands. Electronic address: m.hulsman@tudelft.nl.
authors.forename: Marc
authors.initials: M
authors.lastname: Hulsman
authors.affiliation: MIRA Institute for Biomedical Technology and Technical Medicine, Department of Tissue Regeneration, University of Twente, P.O. Box 217, Enschede 7500 AE, The Netherlands; MIRA Institute for Biomedical Technology and Technical Medicine, Department of Biomaterials Science and Technology, University of Twente, P.O. Box 217, Enschede 7500 AE, The Netherlands.
authors.forename: Frits
authors.initials: F
authors.lastname: Hulshof
authors.affiliation: MIRA Institute for Biomedical Technology and Technical Medicine, Department of Tissue Regeneration, University of Twente, P.O. Box 217, Enschede 7500 AE, The Netherlands.
authors.forename: Hemant
authors.initials: H
authors.lastname: Unadkat
authors.affiliation: Materiomics BV, Professor Bronkhorstlaan 10 - gebouw 48, 3723MB Bilthoven, The Netherlands.
authors.forename: Bernke J
authors.initials: BJ
authors.lastname: Papenburg
authors.affiliation: MIRA Institute for Biomedical Technology and Technical Medicine, Department of Biomaterials Science and Technology, University of Twente, P.O. Box 217, Enschede 7500 AE, The Netherlands.
authors.forename: Dimitrios F
authors.initials: DF
authors.lastname: Stamatialis
authors.affiliation: MIRA Institute for Biomedical Technology and Technical Medicine, Department of Tissue Regeneration, University of Twente, P.O. Box 217, Enschede 7500 AE, The Netherlands.
authors.forename: Roman
authors.initials: R
authors.lastname: Truckenmüller
authors.affiliation: MIRA Institute for Biomedical Technology and Technical Medicine, Department of Tissue Regeneration, University of Twente, P.O. Box 217, Enschede 7500 AE, The Netherlands.
authors.forename: Clemens
authors.initials: C
authors.lastname: van Blitterswijk
authors.affiliation: MIRA Institute for Biomedical Technology and Technical Medicine, Department of Tissue Regeneration, University of Twente, P.O. Box 217, Enschede 7500 AE, The Netherlands; Laboratory for Cell Biology-inspired Tissue Engineering, Merln Institute, Maastricht University, Minderbroedersberg 4-6, Maastricht 6211 LK, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: de Boer
authors.affiliation: Delft Bioinformatics Lab, Delft University of Technology, Mekelweg 4, Delft 2628 CD, The Netherlands.
authors.forename: Marcel J T
authors.initials: MJ
authors.lastname: Reinders
mesh_terms: D053144:Cell Nucleus Shape; D048430:Cell Shape; D003198:Computer Simulation; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D013499:Surface Properties
keywords: Cell morphology; Interface; Mesenchymal stem cell; Modelling; Surface topography