Determination of mitochondrial lipid packing in healthy and cancerous cell lines

线粒体凋亡的调控对哺乳动物细胞的生理发育和组织健康至关重要。与程序性细胞死亡背道而驰会导致一系列并发症，包括但不限于癌症。然而，这种凋亡机制可以被用来特异性地针对癌细胞的线粒体，而不损害周围的健康细胞。传统的癌症治疗方法使用高度细胞毒剂与放射疗法相结合，对癌细胞和非肿瘤细胞起作用，消除或减少肿瘤生长。不幸的是，这些传统的方法和药物(例如DNA嵌入剂)具有遗传毒性，并有可能导致更多的癌症在以后的生活中表现出来。因此，从根本上了解线粒体的异同，可以为健康研究人员开发更有效的抗癌药物提供必要的基础。我们建议使用甚小角度中子散射(VSANS)来比较来自多个细胞类型的健康和癌症线粒体的线粒体结构。VSANS为生物体系的研究提供了许多优点，因为中子散射对生物膜中脂类中常见的轻元素很敏感。此外，vSANS的使用将允许直接观察线粒体从分子组织到它们在自然水环境中的完整尺寸(2微米)。该项目将回答关于健康细胞和癌细胞之间的组成和结构差异的关键问题，最终刺激SANS的新的应用和研究途径，以阐明癌症治疗的机制。

Regulation of mitochondrial apoptosis is essential for physiological development and tissue health inmammalian cells. Diverging from programmed cell death can lead to an array of complications including, but not limited to, cancer. However, this apoptotic mechanism can be exploited to specifically target the mitochondria of cancerous cells, while leaving surrounding healthy cells unscathed. Conventional cancer treatments use highly cytotoxic agents in combination with radiation therapy that act on both cancerous and non-cancerous cells eliminating or reducing tumor growth. Unfortunately, these traditional methods and drugs (e.g., DNA intercalating agents) are genotoxic and have the potential to lead to the manifestation of additional cancers later in life. Thus, a fundamental understanding of similarities and differences in mitochondria can provide health researchers the necessary foundation to develop more effective anti-cancer agents.We propose to use very small angle neutron scattering (vSANS) to compare the mitochondrial structure of healthy and cancerous mitochondria from multiple cell types. vSANS offers many advantages for the study of biological systems as neutron scattering is sensitive to light elements commonly found in lipids in biological membranes. Further, the use of vSANS will allow for the direct observation of mitochondria from the molecular organization to their full size (2 microns) in their native aqueous environment.This project will answer key questions about composition and structural differences between healthy andcancer cells ultimately stimulating a new application and research avenue for SANS to shed light on themechanism of cancer therapeutics.