The aim of this paper is to further develop mathematical models for bleb formation in cells, including cell-membrane interactions with linker proteins. This leads to nonlinear reaction-diffusion equations on a surface coupled to fluid dynamics in the bulk. We provide a detailed mathematical analysis and investigate some singular limits of the model, connecting it to previous literature. Moreover, we provide numerical simulations in different scenarios, confirming that the model can reproduce experimental results on bleb initation. Cell blebbing, Surface PDEs, Fluid-Structure Interaction, Free Boundary Problems. T for the symmetrised gradient. The set of k-times, k ≥ 0, weak differentiable, X-valued functions, where X is a vector space, on some open set Ω ⊆ R 3 is H k (Ω, X). We will also employ the subspaces of mean-value-free functions:of functions with time-constant mean value:T ∈ [0, ∞), of solenoidals functions:, and the traces of solenoidal functions: