The project aims at developing the picosecond ultrasonic technique (PU) as a non-contact and non-invasive mean to perform quantitative non-invasive imaging of single cell adhesion on a functionalized biomaterial surface. The adhesion of living cells on biocompatible substrates plays a crucial role in tissue response to implanted devices and tissue regeneration, and influences cell proliferation and differentiation. In order to optimize implants, it is therefore vital to understand and control cell adhesion. Yet, measuring non-invasively adhesive properties of biological cells at a sub-micron scale remains a challenge. None of the existing techniques can provide such quantitative knowledge. In our experimental situation, the cell will adhere on one side of a thin functionalized titanium film, and the laser will be focused on the other side. Absorption of femtosecond laser pulses will launch GHz acoustic waves in the film. Thus, using PU as a non-contact and non-invasive mean, we will measure the acoustic reflection coefficient at the biomaterial-cell interface directly. This acoustic reflection coefficient can be merely converted into an interfacial stiffness, representative of the cell-biomaterial bonding state. In addition, using the fast imaging set-up we have recently patented, measurement time has been reduced by a factor 10000. Introduction of this imaging device in the new set-up will allow the acquisition of adhesion maps in a convenient duration with a sub-micron resolution. The proposed technique is thus unique since it is non-invasive, yields direct mechanical quantification of the cell-biomaterial contact, and allows imaging with a submicron resolution. To put the project on solid physical grounds, we first analyze the well-controlled chemically-induced adhesion of biomimetic objects. We consider model polymer microcapsules to calibrate the experiments, before moving on to cell-mediated adhesion. This grounding stage is performed before the beginning of the project supported by ANR, with another funding (PEPS CNRS/Idex Bordeaux). Regarding the ANR project itself, in a secured step by step approach, we will start with the adhesion of model cells. Monocytes will be considered first since their size, shape and uniform adhesion resembles that of microcapsules. Their small size will allow performing 1D scans along a line across single cell adhesion area with simple modifications of the usual set-up. Then oscteoclast cells will be considered as more advanced model cells. Their adhesion is mediated through an adhesion belt of podosomes yielding a non-homogeneous annular adhesion at the periphery of the cell-material interface. For quantitative imaging purpose we will perform the adaptation of a new imaging device to map the acoustic reflection coefficient in 2D. Notably, femtosecond laser beams will be introduced in a modified commercial microscope allowing simultaneous fluorescent imaging. The comparison of the 2D opto-acoustic images of the osteoclasts with qualitative fluorescent images should prove the ability of our technique to measure and image heterogeneous cell adhesion. We will then be able to achieve the quantitative imaging of highly heterogeneous cell adhesion at a sub-cell scale. Human osteoblast cells will be grafted on titanium surfaces functionalized with different peptide concentrations. Both the variation of the adhesion and of the cell structure at the focal points of adhesion will be acoustically imaged with a sub-micron resolution. These quantitative measurements will be of a great interest to understand cell-materials interactions. They should notably allow optimizing the density of peptides to be grafted on the biomaterial surface. Moreover, measurements of both cell adhesion and compressibility should allow analysing the cytoskeleton modification and its correlation to cell signalling pathways.