Matic Katarina, Krishnan Nimisha, Frank Eric, Arellano Michael, Sriram Aditya, Das Moumita, Valentine Megan T, Rust Michael J, Robertson-Anderson Rae M, Ross Jennifer L
Department of Physics and Biophysics, University of San Diego, USA.
Department of Physics, Syracuse University, USA.
Soft Matter. 2025 Jun 19;21(24):4792-4806. doi: 10.1039/d4sm01527d.
Incorporating cells within active biomaterial scaffolds is a promising strategy to develop forefront materials that can autonomously sense, respond, and alter the scaffold in response to environmental cues or internal cell circuitry. Using dynamic biocompatible scaffolds that can self-alter their properties crosslinking and motor-driven force-generation opens even greater avenues for actuation and control. However, the design principles associated with engineering active scaffolds embedded with cells are not well established. To address this challenge, we design a dynamic scaffold material of bacteria cells embedded within a composite cytoskeletal network of actin and microtubules that can be passively or actively crosslinked by either biotin-streptavidin or multimeric kinesin motors. Using quantitative microscopy, we demonstrate the ability to embed cells of volume fractions 0.4-2% throughout the network without compromising the structural integrity of the network or inhibiting crosslinking or motor-driven dynamics. Our findings suggest that both passive and active crosslinking promote entrainment of cells within the network, while depletion interactions play a more important role in uncrosslinked networks. Moreover, we show that large-scale structures emerge with the addition of cell fractions as low as 0.4%, but these structures do not influence the microscale structural length scale of the materials. Our work highlights the potential of our composite biomaterial in designing autonomous materials controlled by cells, and provides a roadmap for effectively coupling cells to complex composite materials with an eye towards using cells as factories to program material modifications.
将细胞整合到活性生物材料支架中是开发前沿材料的一种有前景的策略，这些材料能够自主感知、响应并根据环境线索或内部细胞信号改变支架。使用能够自我改变其性质（交联和电机驱动的力产生）的动态生物相容性支架，为驱动和控制开辟了更广阔的途径。然而，与设计嵌入细胞的活性支架相关的设计原则尚未完全确立。为应对这一挑战，我们设计了一种动态支架材料，它由嵌入肌动蛋白和微管复合细胞骨架网络中的细菌细胞组成，该网络可以通过生物素 - 链霉亲和素或多聚驱动蛋白马达进行被动或主动交联。通过定量显微镜，我们证明了能够在整个网络中嵌入体积分数为0.4 - 2%的细胞，而不会损害网络的结构完整性，也不会抑制交联或电机驱动的动力学过程。我们的研究结果表明，被动和主动交联都能促进细胞在网络中的夹带，而耗尽相互作用在未交联的网络中起更重要的作用。此外，我们表明，即使添加低至0.4%的细胞分数也会出现大规模结构，但这些结构不会影响材料的微观结构长度尺度。我们的工作突出了我们的复合生物材料在设计由细胞控制的自主材料方面的潜力，并为有效地将细胞与复杂复合材料耦合提供了路线图，着眼于将细胞用作编程材料改性的工厂。
