Pokhrel Aawaz R, Steinbach Gabi, Krueger Adam, Day Thomas C, Tijani Julianne, Ng Siu Lung, Hammer Brian K, Yunker Peter J
bioRxiv. 2023 Nov 17:2023.11.17.567592. doi: 10.1101/2023.11.17.567592.
Bacteria often attach to surfaces and grow densely-packed communities called biofilms. As biofilms grow, they expand across the surface, increasing their surface area and access to nutrients. Thus, the overall growth rate of a biofilm is directly dependent on its "range expansion" rate. One factor that limits the range expansion rate is vertical growth; at the biofilm edge there is a direct trade-off between horizontal and vertical growth-the more a biofilm grows up, the less it can grow out. Thus, the balance of horizontal and vertical growth impacts the range expansion rate and, crucially, the overall biofilm growth rate. However, the biophysical connection between horizontal and vertical growth remains poorly understood, due in large part to difficulty in resolving biofilm shape with sufficient spatial and temporal resolution from small length scales to macroscopic sizes. Here, we experimentally show that the horizontal expansion rate of bacterial colonies is controlled by the contact angle at the biofilm edge. Using white light interferometry, we measure the three-dimensional surface morphology of growing colonies, and find that small colonies are surprisingly well-described as spherical caps. At later times, nutrient diffusion and uptake prevent the tall colony center from growing exponentially. However, the colony edge always has a region short enough to grow exponentially; the size and shape of this region, characterized by its contact angle, along with cellular doubling time, determines the range expansion rate. We found that the geometry of the exponentially growing biofilm edge is well-described as a spherical-cap-napkin-ring, i.e., a spherical cap with a cylindrical hole in its center (where the biofilm is too tall to grow exponentially). We derive an exact expression for the spherical-cap-napkin-ring-based range expansion rate; further, to first order, the expansion rate only depends on the colony contact angle, the thickness of the exponentially growing region, and the cellular doubling time. We experimentally validate both of these expressions. In line with our theoretical predictions, we find that biofilms with long cellular doubling times and small contact angles do in fact grow faster than biofilms with short cellular doubling times and large contact angles. Accordingly, sensitivity analysis shows that biofilm growth rates are more sensitive to their contact angles than to their cellular growth rates. Thus, to understand the fitness of a growing biofilm, one must account for its shape, not just its cellular doubling time.
细菌常常附着于表面并形成紧密堆积的群落,即生物膜。随着生物膜的生长,它们会在表面扩展,增加其表面积并获取更多营养。因此,生物膜的总体生长速率直接取决于其“范围扩展”速率。限制范围扩展速率的一个因素是垂直生长;在生物膜边缘,水平生长和垂直生长之间存在直接的权衡——生物膜向上生长得越多,向外生长得就越少。因此,水平生长和垂直生长的平衡会影响范围扩展速率,至关重要的是,还会影响生物膜的总体生长速率。然而,水平生长和垂直生长之间的生物物理联系仍知之甚少,这在很大程度上是由于难以从小长度尺度到宏观尺寸以足够的空间和时间分辨率解析生物膜的形状。在此,我们通过实验表明,细菌菌落的水平扩展速率受生物膜边缘的接触角控制。利用白光干涉测量法,我们测量了生长中菌落的三维表面形态,发现小菌落出人意料地可以很好地用球冠来描述。在后期,营养物质的扩散和摄取会阻止高大的菌落中心呈指数增长。然而,菌落边缘始终有一个足够短的区域能够呈指数增长;该区域的大小和形状由其接触角以及细胞倍增时间决定,进而决定了范围扩展速率。我们发现,呈指数生长的生物膜边缘的几何形状可以很好地用球冠 - 餐巾环来描述,即中心有一个圆柱形孔的球冠(此处生物膜过高而无法呈指数生长)。我们推导出了基于球冠 - 餐巾环的范围扩展速率的精确表达式;此外,一阶近似下,扩展速率仅取决于菌落接触角、呈指数生长区域的厚度以及细胞倍增时间。我们通过实验验证了这两个表达式。与我们的理论预测一致,我们发现细胞倍增时间长且接触角小的生物膜实际上比细胞倍增时间短且接触角大的生物膜生长得更快。相应地,敏感性分析表明,生物膜生长速率对其接触角的敏感性高于对其细胞生长速率的敏感性。因此,要了解生长中生物膜的适应性,必须考虑其形状,而不仅仅是其细胞倍增时间。