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Circular Adhesion Substrates Inhibiting Cell Polarization and Proliferation via Graded Texture of Geometric
Yifeng Nie1, Xi Lu1,2, Yuting Zhu3
1CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, P. R. China.
Abstract:
Most melanomas that occur on the skin surface originate from a newly formed nevus and grow outward in a circular pattern and metastasize from the nevus center. Herein, a circular microfabricated substrate is constructed to explore the growth behavior of melanoma cells. Modeling software is used to calculate appropriate parameters, including shape and size, and then the substrates are processed with microfabrication technologies. The results show that the melanoma cells on the circular adhesion substrate are oval and are significant changes in cell spread length, nuclei, area, aspect ratio, Young's modulus, and orientation angles, indicating inhibition of cell polarization. Moreover, three different layers from circular adhesion substrates are selected to construct new substrates, which indicates that the polarization degree of cells is closely related to the number of micropillar arrays on the circular geometric substrate. In addition, flow cytometry demonstrates that the circular substrate reduced the transition from resting/gap 1 phase (G0/G1) to synthesis phase (S phase), thereby decreasing DNA synthesis and proliferation, reminding a potential method for treatment strategy. More importantly, the circular adhesion substrate influences the integrin signaling pathway, which has a potential application and research prospect in the treatment of melanoma.
Insights
This study developed a circular microfabricated substrate to investigate melanoma cell growth. Findings show it inhibits cell polarization and proliferation, suggesting a novel melanoma treatment strategy.
Area of Science:
- Biomaterials Science
- Cancer Biology
- Cellular Mechanics
Background:
- Melanoma typically grows outward from a nevus and metastasizes from the center.
- Understanding melanoma cell behavior is crucial for developing effective treatments.
Purpose of the Study:
- To explore melanoma cell growth dynamics using a novel circular microfabricated substrate.
- To investigate the impact of substrate geometry on cell polarization, proliferation, and signaling pathways.
Main Methods:
- Fabrication of circular microarrays using microfabrication technologies and modeling software.
- Analysis of melanoma cell morphology, mechanical properties (Young's modulus), and orientation on substrates.
- Flow cytometry to assess cell cycle progression (G0/G1 to S phase transition).
- Investigation of the integrin signaling pathway.
Main Results:
- Melanoma cells exhibited altered morphology (oval shape) and reduced polarization on circular substrates.
- Cell proliferation, DNA synthesis, and transition from G0/G1 to S phase were decreased.
- Polarization degree correlated with micropillar array density on the substrate.
- The circular substrate influenced the integrin signaling pathway.
Conclusions:
- Circular microfabricated substrates can inhibit melanoma cell polarization and proliferation.
- Substrate design, specifically micropillar density, affects cell polarization.
- This approach offers a potential new strategy for melanoma treatment by targeting cell signaling pathways.
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