Biocompatibility: Chapter 3

Front 1

The behavior of proteins at surfaces plays a vital role in what?

Back 1

In determining the nature of the tissue-implant interface!

Front 2

Adsorbed proteins affect what 5 things?

Back 2

1. Blood coagulation
2. Complement activation
3. Bacterial and cell adhesion
4. Biomaterial surface properties
5. Biomaterial degradation

Front 3

Larger molecules are more likely to do what? why?

Back 3

Interact with surfaces because they are able to contact the surface at more sites.

Front 4

TRUE OR FALSE: Size is the only determinant when it comes to protein-surface interaction.

Back 4

FALSE. There are other determinants.

Front 5

Because of their hydrophilicity, charged amino acids are generally located where? what does this mean?

Back 5

On the outside of proteins which means they are readily available to interact with surfaces.

Front 6

What is an Isoelectric Point?

Back 6

The pH at which the molecule exhibits 0 charge

Front 7

What are 5 properties of proteins that affect their interaction with surfaces?

Back 7

1. Size
2. Charge
3. Structure
4. Stability
5. Unfolding rate

Front 8

TRUE OR FALSE: Molecules near their isoelectric points generally absorb slower on surfaces.

Back 8

FALSE. They absorb more readily!

Front 9

Less stable proteins can do what in regards to surface interaction?

Back 9

Can unfold to a greater extent and form more contact points with the surface.

Front 10

What 5 properties of Surfaces can affect their interaction with Proteins?

Back 10

1. Topography
2. Composition
3. Hydrophobicity
4. Heterogeneity
5. Potential

Front 11

TRUE OR FALSE: Greater texture exposes more surface area for interaction with proteins.

Back 11

TRUE

Front 12

Chemical makeup of a surface will determine what?

Back 12

The types of intermolecular forces governing interaction with proteins.

Front 13

Do hydrophobic or hydrophilic surfaces bind more protein?

Back 13

Hydrophobic surfaces bind more protein

Front 14

Nonuniformity of surface characteristics results in what?

Back 14

Domains that can interact differently with proteins

Front 15

Surface potential will influence what?

Back 15

The distribution of ions in solution and interaction with proteins

Front 16

At the isoelectric point, reduced electrostatic repulsion between the uncharged adsorbing molecules means what?

Back 16

There can be more proteins to bind to the surface versus themselves.

Front 17

If the conformation of a protein is altered, what can happen?

Back 17

Different amino acids could be exposed on the surface of the protein which could change the way the molecule binds to the surface.

Front 18

Unfolding of a protein is likely to do what?

Back 18

Expose more sites for protein-surface contact.

Front 19

What type of proteins are more likely to unfold more or faster?

Back 19

Less stable proteins or those with less intramolecular cross-linking

Front 20

Unfolding proteins can expose what? What does this cause?

Back 20

Can expose hydrophobic regions that then interact with the surface themselves!

Front 21

What are the 3 categories of surface properties?

Back 21

1. Geometric
2. Chemical
3. Electrical

Front 22

The surface chemical composition will determine what?

Back 22

Which functional species are available for interactions with biomolecules.

Front 23

Patches or domains of different functionality can exist on biomaterial surfaces and can cause what?

Back 23

Can cause different biomolecules to interact differently to the surfaces

Front 24

The combined effects of what 3 things will determine whether interaction with biomolecules is inhanced or hindered?

Back 24

1. Water ions
2. Molecules
3. Net surface potential

Front 25

What is Adsorption?

Back 25

The process whereby molecules adhere to solid surfaces.

Front 26

What plays a critical role in determining the fate of the tissue-implant interface?

Back 26

The accumulation of protein on biomaterial surfaces!

Front 27

Adsorption depends on what?

Back 27

1. protein and surface properties
2. protein availability

Front 28

Molecules can be brought to the surface by what 4 mechanisms?

Back 28

1. Diffusion
2. Thermal convection
3. Flow
4. Coupled transport like the combo of convection and diffusion

Front 29

What 3 variables are important in determining the arrival of protein molecules at a surface?

Back 29

1. Concentration
2. Velocity
3. Molecular size

Front 30

Higher diffusion coefficient is inversely related to what?

Back 30

Molecular size

Front 31

Once present at the surface, protein molecules can interact with the substrate via what 3 interactions?

Back 31

1. Ionic bonding
2. Hydorphobic interactions
3. Charge-transfer interactions

Front 32

TRUE OR FALSE: Hydrogen bonding plays a major role in protein-surface interactions.

Back 32

FALSE. It doesn't play a major role.

Front 33

Even with a solution containing a single type of protein, a layer of adsorbed protein is likely to be what?

Back 33

Heterogeneous

Front 34

As the surface becomes occupied, what happens?

Back 34

There is less surface available for adsorption of subsequent protein molecules thus molecules in different orientations might be able to bind or may not be able to.

Front 35

Depending on the orientation of adsorbed molecules, what can happen?

Back 35

Further active sites may be inaccessible!

Front 36

What is Desorption?

Back 36

The reverse of adsorption: molecules previously bound to a surface detach and return to the bulk phase.

Front 37

For desorption to occur, what must happen?

Back 37

All contacts between protein and surface must be simultaneously broken!

Front 38

Although well characterized for small molecules such as gases, desorption of proteins is what?

Back 38

Slow or nonexistent.

Front 39

Unless what is done, protein adsorption is largely irreversible because of the requirement of simultaneous dissociation of bonds?

Back 39

Unless there are dramatic changes in the interfacial environments like increased ionic strength, lowered pH, use of chaotropic agents or detergents!

Front 40

The difficulty or improbability of simultaneous disruption of all contacts is increased further by what? why?

Back 40

Large proteins because they can form a greater number of bonds with the surface!

Front 41

For a molecule of fibrinogen to desorb, how many bonds must be broken simultaneously?

Back 41

All 703!

Front 42

TRUE OR FALSE: Proteins do not experience structural alterations during interaction with solid surfaces.

Back 42

FALSE.

Front 43

TRUE OR FALSE: Adsorbed proteins generally retain at least *some* of their biological activity.

Back 43

TRUE

Front 44

What is the first mode of conformational change that can occur when proteins adsorb to solid surfaces?

Back 44

Protein molecules can undergo time-dependent molecular spreading where the protein unfolds and further interacts with the substrate.

Front 45

What is the second mode of conformational change that can occur when proteins adsorb to solid surfaces?

Back 45

Altered conformation can result from changes in the bulk solution concentration

Front 46

At low concentration, is there abundant surface area available for each protein molecule?

Back 46

Yes!

Front 47

At high bulk concentrations, the amount of surface per molecule increases or decreases? What does this mean?

Back 47

Surface per molecule decreases which leads to decreased unfolding and fewer contacts on the surface.

Front 48

When a surface is exosed to a multicomponent solution, certain molecules will do what?

Back 48

Will be preferentially deposited from the bulk

Front 49

What two variables are important to the adsorption of proteins in an multicomponent solution?

Back 49

1. Affinity
2. Kinetic Factors

Front 50

What kind of proteins will adsorb first in multicomponent solutions?

Back 50

1. Proteins with high concentration
2. Small proteins with large diffusion coefficient

Front 51

Exchange of proteins in multicomponent solutions results from what?

Back 51

Competition of the various proteins on and around the substrate!

Front 52

The first molecule is released from the surface when what happens?

Back 52

When all of its contacts with the substrate become occupied by the new molecule.

Front 53

Exchange of proteins proceeds until what happens?

Back 53

Until the surface is populated with proteins having strong interaction with the substrate.

Front 54

What is the Vroman effect?

Back 54

The hierarchical series of collision, adsorption and exchange processes in regards to protein and surface interactions.

Front 55

On the basis of mass transport considerations, which proteins will be the first to arrive at the surface?

Back 55

Proteins present at the highest concentration!

Front 56

In Blood-Surface interactions, what is protein dominates initial interactions with the surface?

Back 56

Albumin!

Front 57

Why does IgG have a slower rate of arrival on the surface?

Back 57

It has a lower concentration in the blood and is a larger protein.

Front 58

If its molecules have a greater affinity for the surface, what can IgG do?

Back 58

It can exchange with bound albumin molecules on the surface!

Front 59

Adsorption of proteins involved in blood clotting such as fibrinogen and factor XII have great importance in determining what?

Back 59

Tissue-implant interactions!

Front 60

The longer a protein molecule resides on a surface means what?

Back 60

The less likely it is to be desorbed or exchanged by other molecules!

Front 61

In multicomponent solutions, such as real body fluids, proteins do what? What does this result in?

Back 61

Proteins compete for surface binding sites resulting in a series of collision, adsorption, and exchange processes on the biomaterial.

Front 62

Explain how the presence of disulfide bonds within a protein influences its ability to adsorb to surfaces.

Back 62

Disulfide bridges are covalent bonds that stabilize the structure of a protein and thus are less able to unfold on a surface and thus fewer binding sites would be brought into proximity to the surface to enable bonding.

Front 63

In a single-component solution, what is likely to occur?

Back 63

Intermolecular repulsion between the identical molecules is likely to occur

Front 64

In desorption, does the protein molecule leave the surface without influence from other proteins?

Back 64

YES!

Front 65

With displacement, what replaces the molecule?

Back 65

Another molecule of the same kind!