In this work we aim to fundamentally understand the adhesive contact and the molecular interactions between synthetic adhesive systems in wet conditions. Specifically, we are addressing key questions concerning how the polymer architecture (random vs side graft chains), the degree of functionalization and the ratio between charged and uncharged moieties affect the microscopic adhesive performances underwater, using polymer brushes as model system. We report the design, the investigation and the comparison of adhesive properties of thermo- and pH-responsive adhesive systems based on random and graft copolymer brushes containing poly(N-isopropylacrylamide) (PNIPAm) and poly(acrylic acid) (PAA) units. Swelling properties and surface charge density at the interface were investigated using spectroscopic ellipsometry and streaming potential/streaming current measurements, respectively. The change in wetting properties in the designed systems upon variation of temperature and ionic strength has been studied by captive bubble technique underwater. Adhesion properties were studied in situ in aqueous solutions at different temperatures and at different ionic strength using AFM colloidal probe against substrates with varied wetting properties as well as surface charge.