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Role of Protein Adsorption - Coggle Diagram
Role of Protein Adsorption
Protein Info
AKA Polypeptides
Organic Compounds
Made of
Amino Acids
arranged in a linear chain & folded into a globular form
Amino Acids
Human body requires 20 standard Amino Acids to grow, repair tissues, and function properly
Divided into 3 main categories:
Essential Amino Acids
(9)
The body cannot manufacture these.
Must be obtained through diet or supplements
Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine
Nonessential Amino Acids
(5)
Body can synthesize these internally
Alanine, Asparagine, Aspartic Acid, Glutamic Acid, Serine
Conditionally Essential Amino Acids
(6)
Normally Non-essential, but become essential during periods of illness, stress, rapid growth, or trauma
Arginine, Cysteine, Glutamine, Glycine, Proline, Tyrosine
Protein Conformation: 4 Structures
Primary
Amino Acid
Sequence
Secondary
Regularly repeating local structures stabilized by hydrogen bonds
Tertiary
Overall shape of a single protein molecule
Quaternary
Structure formed by several protein molecules
Called polypeptide chains
Importance of Studying Proteins
Key mechanism in ensuring successful implantation of biomaterials
Understanding how blood proteins interact w/ synthetic biomaterial surfaces
Albumin, Fibrinogen, & Fibronectin
Typically, when a biomaterial is inserted in living tissue, proteins & other molecules adsorb to the surface
This protein layer will mediate the interaction of the biomaterial with the living world
Plasma Proteins
Proteins present in blood plasma
Serve many different functions
Transport of lipids, hormones, vitamins, & metals in the circulatory system
Regulation of acellular activity & functioning
In the immune system
Act as enzymes, complement components, protease inhibitor or kinin precursors
Blood contains 2 main kinds of proteins
Albumin
Keep the blood from leaking out of blood vessels
Carry some medicines & other substances through the blood
Important for tissue growth & healing
More than half of the protein in blood serum
Globulins
4 Types:
Alpha-1
High-Density Lipoprotein (HDL)
"Good cholestestorol" is included in this fraction
Alpha-2
Haptoglobin
Binds to hemoglobin
Included in this fraction
Beta
Help carry substances, such as iron, through the bloodstream & help fight infection
Gamma
Antibodies
Help prevent & fight infection
Bind to foreign substances & destroy them
Both carry substances through bloodstream
Hormones, Enzymes, & Antibodies
Help body produce substances it needs to function
Protein Interactions
Biomaterials Interactions
Water-Surface
Water molecules & ions from body fluids interact w/ biomaterial surface within milliseconds
Forms a hydration shell that depends on the material's chemical & physical properties
Protein Adsorption (Conditioning Film)
Free proteins from blood or interstitial fluid land on surface within seconds to minutes
Smaller, fast-moving proteins arrive first, such as Albumin
Later replaced over time by larger or higher-affinity proteins
Called the Vroman effect
Protein Conformation & Structural Alteration
Once adsorbed, protein molecules can change their 3D shape
Due to surface energy, hydrophobic interactions, or electrostatic forces
This unfolding can expose hidden active binding cites that cells can recognize
Cell Attachment & Downstream Biological Response
Cells do not touch bare biomaterial
Instead, they bind to newly formed protein layer via specific cell-surface receptors called integrins
This dictates whether the body integrates the material (bone growth, tissue healing) or rejects it (inflammation, blood clotting, or fibrous encapsulation)
Protein-Surface Interactions
Protein adsorption characteristics can be controlled by changing substrate surface parameters
Surface Chemistry
Plays an important role in determining adsorbed protein conformation
As well as rates of adsorption & the amount of protein adsorbed
Through interaction between functional groups & those of the protein itself
Chemical nature of the surface can be modified to induce greater protein-surface affinity
By either electrostatic or hydrophobic interactions
Topography
Architecture of the surface may be used to manipulate protein shape & form upon adsorption
Atomic force microscopy & SCM to determine topography
Topography on the order of nanometres has been shown to impact the conformation of bound proteins
Architecture of the surface may be used to manipulate protein shape & form upon adsorption
Not fully explored, but a critical factor in understanding scaffold architecture
In-Vivo Responses
Most info is based on
in-vitro
studies
Most in-vivo studies are conducted for applications like:
Wound healing
Osseointegration
Fate of implants is determined by the response of cells to the implant material's surface
Positive, like tissue regen & osseointegration
Negative, like chronic inflammation & fibrous encapsulation
Fibrous encapsulation = immune response where body surrounds foreign object in scar tissue
Initial presentation of a foreign material to cells is a layer of spontaneously adsorbed proteins
Their composition & bioactivity provide a biological interpretation of underlying physiochemical properties
Adsorption of proteins such as vitronectin and fibronectin is a key factor several processes
Interaction of fibrinogen with implant surfaces is critical in-vivo
It has involvement in clot formation & platelet activation
Only in early stages of understanding
Understanding composition of the interface at the relevant time point is crucial for predicting or controlling living tissue response to implanted surfaces
Understanding formation & function of the adsorbed protein layer would provide important link btwn biomaterial surface properties & biological responses
Mechanisms of Protein Adsorption
Proteins adsorb in differing quantities, densities, conformations, & orientations
Adsorb rapidly & become more deformed on surfaces w/ decreasing wettability
Minimizes contact w/ the aqueous phase
Charged protein regions can interact w/ oppositely charged surfaces
Primary adsorption depends on:
Surface chemistry
Surface-protein interactions are not well understood
Plays a fundamental role in protein adsorption
Properties of protein over-layers can be altered by the underlying surface chemistry of a material
Surface topography
Surface physical characteristics
Steps
(Partial) dehydration of protein & sorbent surfaces
Sorbent = insoluble material that recovers liquids or gases through absorption
Redistribution of charged groups in the interface
Conformational changes in the protein molecule
Mediation of Biomaterial-Cell Interactions by Adsorbed Proteins
2 Key determinants of protein-mediated cell response:
Adsorption Profile
Which proteins are adsorbed & in what quantities
Protein Bioactivity
Functionality, as determined by conformation, orientation, etc.
In vitro studies generally demonstrate favourable cell responses to charged, hydrophilic surfaces
This corresponds to superior adsorption & bioactivity of adhesion proteins