CAREER: Nonlinear Infrared Studies of Biomolecular Coacervation

在化学系化学结构，动力学和机制A（CSDM-A）计划的支持下，圣母大学的Arnaldo塞拉诺正在使用先进的基于激光的光谱技术来研究由不同相组成的液滴表面和内部的蛋白质结构和相互作用。蛋白质在生物有机体中“自发地”折叠成定义明确的三维结构，并且可能参与细胞组织。塞拉诺小组正在推进二维红外光谱和显微镜方法，这些方法可以以高灵敏度和特异性检测蛋白质折叠和形状的变化。通过使用控制良好的小液滴，可以了解对蛋白质功能和结构的影响。通过这一系列实验研究所取得的发现可以更好地理解蛋白质结构，随后可以调节蛋白质结构以实现目标功能。塞拉诺小组还将通过一个关于先进超快光谱和成像的区域研究生研讨会与其他研究人员合作，以及为大学生开发基于网络的开放源代码化学动力学软件平台。塞拉诺小组将使用超快红外光谱工具，包括二维红外（2D-IR）和红外和频（IRSF）光谱。生物系统中结构单元的组织，例如在LLP期间由蛋白质形成的结构单元，被假设代表了细胞组织的普遍机制，其中相变对于局部观察到的蛋白质二级结构和水合作用水平至关重要。蛋白质和其他生物聚合物的化学物理将作为新相的形式进行研究。2D-IR和IRSF光谱将用于监测液-液相分离液滴内蛋白质结构、动力学和溶剂化的原位表征。这些光谱工具的进步加上LLPS液滴系统有可能创造新的生物物理测量方法，能够揭示相分离如何诱导蛋白质二级结构和功能的变化。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

With support from the Chemical Structure, Dynamics, and Mechanisms A (CSDM-A) Program in the Division of Chemistry, Arnaldo Serrano of the University of Notre Dame is using advanced laser-based spectroscopic techniques to investigate protein structure and interactions both in and on the surface of droplets that are composed of distinct phases. Proteins fold into well-defined three dimensional structures 'spontaneously' in biological organisms and are likely involved in cellular organization. The Serrano group is advancing two-dimensional infrared spectroscopy and microscopy methods that can detect changes in protein folding and shape with high sensitivity and specificity. By also using small well-controlled droplets, impacts on protein function and structure can be learned. Discoveries made through this line of experimental inquiry could lead to better understanding of protein structure that could be subsequently modulated to achieve targeted functions. The Serrano group will also engage with other researchers through a regional graduate student workshop on advanced ultrafast spectroscopy and imaging, as well as in the development of an open-source web-based chemical kinetics software platform for undergraduates.The Serrano group will study liquid-liquid phase separation (LLPS) or coacervation using ultrafast infrared spectroscopic tools including two-dimensional infrared (2D-IR) and infrared sum frequency (IRSF) spectroscopies. Organization of building blocks in biological systems such as those that form from proteins during LLPS, are hypothesized to represent a universal mechanism of cellular organization with phase transitions being critical to the level of protein secondary structure and hydration that is locally observed. The chemical physics of proteins and other biopolymers will be studied as new phases form. 2D-IR and IRSF spectroscopies will be used to monitor the in-situ characterization of protein structure, dynamics, and solvation within liquid-liquid phase-separated droplets. The advancement of these spectroscopic tools coupled with LLPS droplet systems has the potential to create new biophysical measurement approaches capable of revealing how phase separation induces variations on the secondary structure and function of proteins.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.