Berengut Jonathan F, Wong Chak Kui, Berengut Julian C, Doye Jonathan P K, Ouldridge Thomas E, Lee Lawrence K
EMBL Australia Node for Single Molecule Science, School of Medical Sciences, University of New South Wales Sydney 2052, Australia.
Physical & Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, United Kingdom.
ACS Nano. 2020 Dec 22;14(12):17428-17441. doi: 10.1021/acsnano.0c07696. Epub 2020 Nov 24.
Biology demonstrates how a near infinite array of complex systems and structures at many scales can originate from the self-assembly of component parts on the nanoscale. But to fully exploit the benefits of self-assembly for nanotechnology, a crucial challenge remains: How do we rationally encode well-defined global architectures in subunits that are much smaller than their assemblies? Strain accumulation geometric frustration is one mechanism that has been used to explain the self-assembly of global architectures in diverse and complex systems . Here we take the next step and use strain accumulation as a rational design principle to control the length distributions of self-assembling polymers. We use the DNA origami method to design and synthesize a molecular subunit known as the PolyBrick, which perturbs its shape in response to local interactions flexible allosteric blocking domains. These perturbations accumulate at the ends of polymers during growth, until the deformation becomes incompatible with further extension. We demonstrate that the key thermodynamic factors for controlling length distributions are the intersubunit binding free energy and the fundamental strain free energy, both which can be rationally encoded in a PolyBrick subunit. While passive polymerization yields geometrical distributions, which have the highest statistical length uncertainty for a given mean, the PolyBrick yields polymers that approach Gaussian length distributions whose variance is entirely determined by the strain free energy. We also show how strain accumulation can in principle yield length distributions that become tighter with increasing subunit affinity and approach distributions with uniform polymer lengths. Finally, coarse-grained molecular dynamics and Monte Carlo simulations delineate and quantify the dominant forces influencing strain accumulation in a molecular system. This study constitutes a fundamental investigation of the use of strain accumulation as a rational design principle in molecular self-assembly.
生物学展示了在许多尺度上近乎无限的复杂系统和结构阵列如何源自纳米级组件的自组装。但要充分利用自组装在纳米技术中的优势，一个关键挑战仍然存在：我们如何在比其组装体小得多的亚基中合理编码明确的全局架构？应变积累和几何受挫是一种已被用于解释各种复杂系统中全局架构自组装的机制。在这里，我们更进一步，将应变积累用作一种合理的设计原则来控制自组装聚合物的长度分布。我们使用DNA折纸方法设计并合成了一种称为PolyBrick的分子亚基，它会响应局部相互作用和灵活的变构阻断域而改变其形状。这些扰动在聚合物生长过程中在其末端积累，直到变形变得与进一步延伸不相容。我们证明，控制长度分布的关键热力学因素是亚基间结合自由能和基本应变自由能，这两者都可以在PolyBrick亚基中合理编码。虽然被动聚合产生几何分布，对于给定均值其统计长度不确定性最高，但PolyBrick产生的聚合物接近高斯长度分布，其方差完全由应变自由能决定。我们还展示了应变积累原则上如何产生随着亚基亲和力增加而变得更紧密的长度分布，并接近聚合物长度均匀的分布。最后，粗粒度分子动力学和蒙特卡罗模拟描绘并量化了影响分子系统中应变积累的主导力。这项研究构成了对应变积累作为分子自组装中一种合理设计原则的基础研究。
