Engineering the Cellular Microenvironment: Integrating Three-Dimensional Nontopographical and Two-Dimensional Biochemical Cues for Precise Control of Cellular Behavior

ACS Nano, vol. 18, pp. 19064–19076

Abstract

The development of biomaterials capable of regulating cellular processes and guiding cell fate decisions has broad implications in tissue engineering, regenerative medicine, and cell-based assays for drug development and disease modeling. Recent studies have shown that three-dimensional (3D) nanoscale physical cues such as nanotopography can modulate various cellular processes like adhesion and endocytosis by inducing nanoscale curvature on the plasma and nuclear membranes. Two-dimensional (2D) biochemical cues such as protein micropatterns can also regulate cell function and fate by controlling cellular geometries. Development of biomaterials with precise control over nanoscale physical and biochemical cues can significantly influence programming cell function and fate. In this study, we utilized a laser-assisted micropatterning technique to manipulate the 2D architectures of cells on 3D nanopillar platforms. We performed a comprehensive analysis of cellular and nuclear morphology and deformation on both nanopillar and flat substrates. Our findings demonstrate the precise engineering of single cell architectures through 2D micropatterning on nanopillar platforms. We show that the coupling between the nuclear and cell shape is disrupted on nanopillar surfaces compared to flat surfaces. Furthermore, our results suggest that cell elongation on nanopillars enhances nanopillar-induced endocytosis. We believe our platform serves as a versatile tool for further explorations into programming cell function and fate through combined physical cues that create nanoscale curvature on cell membranes and biochemical cues that control the geometry of the cell.

Authors 14

1. Einollah Sarikhani

   University of California San Diego

   Affiliation as printed

   Department of NanoEngineering, University of California San Diego, La Jolla ,California 92093, United States

2. Dhivya Pushpa Meganathan

   University of California San Diego

   Affiliation as printed

   Department of NanoEngineering, University of California San Diego, La Jolla ,California 92093, United States

3. Anne‐Kathrine Kure Larsen

   Aarhus University

   Affiliation as printed

   Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C 8000, Denmark

4. Keivan Rahmani

   University of California San Diego

   Affiliation as printed

   Department of NanoEngineering, University of California San Diego, La Jolla ,California 92093, United States

5. Ching‐Ting Tsai

   Stanford University

   Affiliation as printed

   Department of Chemistry, Stanford University, Stanford ,California 94305, United States

6. Chih‐Hao Lu

   Stanford University

   Affiliation as printed

   Department of Chemistry, Stanford University, Stanford ,California 94305, United States

7. Abel Marquez-Serrano

   University of California San Diego

   Affiliation as printed

   Department of NanoEngineering, University of California San Diego, La Jolla ,California 92093, United States

8. Leah Sadr

   University of California San Diego

   Affiliation as printed

   Department of NanoEngineering, University of California San Diego, La Jolla ,California 92093, United States

9. Xiao Li

   Stanford University

   Affiliation as printed

   Department of Chemistry, Stanford University, Stanford ,California 94305, United States

10. Mingdong Dong

    Aarhus University

    Affiliation as printed

    Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C 8000, Denmark

11. Francesca Santoro Aachen Faculty of Electrical Engineering and IT

    RWTH Aachen University · Forschungszentrum Jülich · Center for Advanced Biomaterials for Healthcare

    Affiliation as printed

    Center for Advanced Biomaterials for Healthcare, Tissue Electronics, Instituto Italiano di Tecnologia, Naples 80125, Italy

    Faculty of Electrical Engineering and IT, RWTH, Aachen 52074, Germany

    Institute for Biological Information Processing-Bioelectronics, Forschungszentrum Juelich, Julich 52428, Germany

12. Bianxiao Cui

    Stanford University

    Affiliation as printed

    Department of Chemistry, Stanford University, Stanford ,California 94305, United States

13. Lasse Hyldgaard Klausen corresponding

    Aarhus University

    Affiliation as printed

    Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C 8000, Denmark

14. Zeinab Jahed corresponding

    University of California San Diego

    Affiliation as printed

    Department of Bioengineering, University of California San Diego, La Jolla ,California 92093, United States

    Department of NanoEngineering, University of California San Diego, La Jolla ,California 92093, United States