Shpun Gal, Markus Amos, Farah Nairouz, Zalevsky Zeev, Mandel Yossi
The Alexander Kofkin Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel.
School of Optometry and Visual Science, Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.
Front Cell Dev Biol. 2024 Aug 28;12:1438716. doi: 10.3389/fcell.2024.1438716. eCollection 2024.
Neural cell-electrode coupling is crucial for effective neural and retinal prostheses. Enhancing this coupling can be achieved through surface modification and geometrical design to increase neuron-electrode proximity. In the current research, we focused on designing and studying various biomolecules as a method to elicit neural cell-electrode adhesion via cell-specific integrin mechanisms.
We designed extracellular matrix biomimetic molecules with different head sequences (RGD or YIGSR), structures (linear or cyclic), and spacer lengths (short or long). These molecules, anchored by a thiol (SH) group, were deposited onto gold surfaces at various concentrations. We assessed the modifications using contact angle measurements, fluorescence imaging, and X-ray Photoelectron Spectroscopy (XPS). We then analyzed the adhesion of retinal cells and HEK293 cells to the modified surfaces by measuring cell density, surface area, and focal adhesion spots, and examined changes in adhesion-related gene and integrin expression.
Results showed that YIGSR biomolecules significantly enhanced retinal cell adhesion, regardless of spacer length. For HEK293 cells, RGD biomolecules were more effective, especially with cyclic RGD and long spacers. Both cell types showed increased expression of specific adhesion integrins and proteins like vinculin and PTK2; these results were in agreement with the adhesion studies, confirming the cell-specific interactions with modified surfaces.
This study highlights the importance of tailored biomolecules for improving neural cell adhesion to electrodes. By customizing biomolecules to foster specific and effective interactions with adhesion integrins, our study provides valuable insights for enhancing the integration and functionality of retinal prostheses and other neural implants.
神经细胞与电极的耦合对于有效的神经和视网膜假体至关重要。通过表面修饰和几何设计以增加神经元与电极的接近度可增强这种耦合。在当前的研究中，我们专注于设计和研究各种生物分子，作为一种通过细胞特异性整合素机制引发神经细胞与电极粘附的方法。
我们设计了具有不同头部序列（RGD或YIGSR）、结构（线性或环状）和间隔长度（短或长）的细胞外基质仿生分子。这些分子通过硫醇（SH）基团锚定，以不同浓度沉积在金表面。我们使用接触角测量、荧光成像和X射线光电子能谱（XPS）评估修饰情况。然后，我们通过测量细胞密度、表面积和粘着斑来分析视网膜细胞和HEK293细胞对修饰表面的粘附，并检测粘附相关基因和整合素表达的变化。
结果表明，无论间隔长度如何，YIGSR生物分子均能显著增强视网膜细胞的粘附。对于HEK293细胞，RGD生物分子更有效，尤其是环状RGD和长间隔的情况。两种细胞类型均显示特定粘附整合素以及诸如纽蛋白和PTK2等蛋白质的表达增加；这些结果与粘附研究一致，证实了细胞与修饰表面的特异性相互作用。
本研究强调了定制生物分子对于改善神经细胞与电极粘附的重要性。通过定制生物分子以促进与粘附整合素的特异性和有效相互作用，我们的研究为增强视网膜假体和其他神经植入物的整合及功能提供了有价值的见解。
