Structural investigation of proteins in a lipid context remains challenging due to the unavailability of suitable experimental techniques and sample environments. Two of the most common techniques, for probing protein structures, are X-ray crystallography and nuclear magnetic resonance (NMR). However, for systems involving lipids, these two techniques are not commonly applied, as the presence of a lipid membrane makes crystallization infeasible, and the relatively large size of most lipid-containing systems makes the tumbling too slow for NMR measurements. Therefore, other techniques, such as small angle scattering (SAS) or cryo electron microscopy, have to be used. SAS measurements are performed in physiologically relevant conditions, and measurements on systems containing both proteins and lipids are possible, albeit information is obtained with a relatively low resolution. In this thesis, the membrane protein tissue factor (TF), and its soluble interaction partner Factor VIIa, has been investigated. Upon the rupture of a blood vessel, the formation of the TF:FVIIa complex occurs and initiates the extrinsic blood coagulation pathway. TF:FVIIa recognizes the macromolecular substrate, Factor X (FX) and activates it to FXa, which subsequently participates in the common coagulation pathway, ultimately resulting in blood clotting. The activity of the TF:FVIIa complex, is markedly increased upon the presence of a lipid membrane, and in general, lipid interactions are essential in the blood coagulation system. High-resolution structures of the individual soluble parts of the tertiary TF:FVIIa:FXa complex have been solved, but as the tertiary structure can only be formed in the presence of a lipid bilayer, it is challenging to approach experimentally. In the presented work, the nanodisc (ND), which is asmall lipid bilayer encircled by two amphipathic proteins, was utilized to facilitate the formation of the tertiary complex. Firstly, the production of TF was established in order to obtain the relatively large amounts required for structural studies. In the same study, the incorporation of TF into the developed circularized and solubility enhanced NDs (csND) was optimized. The csNDs were shown to possess higher temporal stability, and to be easy to produce in large amounts. Having TF in a csND enabled functional studies, showing the expected activity of TF. Also SAS measurements were performed both on TF in a csND, but also with FVIIa added, demonstrating the anticipated enlargement of the particle. However, the interaction between the TF:FVIIa complex and FXa is only transitory, and thus we had to deploy an inhibitor, NAPc2, which stabilize the complex, allowing for SAS measurements. In parallel, neutron reflectometry was used to probe the heights of TF and FVIIa on a membrane. These measurements provided the opportunity to evaluate the orientation of both TF and the TF:FVIIa complex on a membrane. Measurements were also performed on FXa, revealing that the FVIIa active site and the cleavage site on FX, are located at the same height, which highlights an essential function of the membrane, and potentially explains part of the membrane induced increase in activity. In summary, this project provided new insights into the lipid-protein interplay in the TF:FVIIa:FXa system. In addition, the first structural data on the quaternary TF:FVIIa:FXa:NAPc2 complex on a lipid bilayer was obtained, laying the foundation for modeling of the TF:FVIIa:FXa complex